{"entity": "researcher", "timestamp": "2026-08-20T19:46:39.918Z", "family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "affiliations": ["Lady Davis Institute, SMBD JGH and Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc"}}, "publications": [{"entity": "publication", "iuid": "81e5144b68534035a091f5a740eb5fe2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/81e5144b68534035a091f5a740eb5fe2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/81e5144b68534035a091f5a740eb5fe2"}}, "title": "Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics.", "authors": [{"family": "Papadopoli", "given": "David", "initials": "D", "orcid": "0000-0002-1248-1839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c2f15cd14b9146fa80dcd759e6e32683.json"}}, {"family": "Palia", "given": "Ranveer", "initials": "R", "orcid": "0000-0003-4265-243X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1ad241b7a3f403f883c2d3d4817ccc9.json"}}, {"family": "Jovanovic", "given": "Predrag", "initials": "P"}, {"family": "Tabari\u00e8s", "given": "S\u00e9bastien", "initials": "S"}, {"family": "Ciccolini", "given": "Emma", "initials": "E"}, {"family": "Sabourin", "given": "Valerie", "initials": "V"}, {"family": "Igelmann", "given": "Sebastian", "initials": "S"}, {"family": "McLaughlan", "given": "Shannon", "initials": "S"}, {"family": "Zhan", "given": "Lesley", "initials": "L"}, {"family": "Kim", "given": "HaEun", "initials": "H"}, {"family": "Chekkal", "given": "Nabila", "initials": "N"}, {"family": "Szkop", "given": "Krzysztof J", "initials": "KJ"}, {"family": "Bertomeu", "given": "Thierry", "initials": "T", "orcid": "0000-0002-5313-7057", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ad1f2a133af4f55a683e1b5dbf09a7a.json"}}, {"family": "Zeng", "given": "Jibin", "initials": "J"}, {"family": "Vassalakis", "given": "Julia", "initials": "J", "orcid": "0009-0000-1261-3638", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bf7fa25855a47dd803b623bff271930.json"}}, {"family": "Afzali", "given": "Farzaneh", "initials": "F"}, {"family": "Mzoughi", "given": "Slim", "initials": "S"}, {"family": "Guccione", "given": "Ernesto", "initials": "E", "orcid": "0000-0001-7764-5307", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c243f84fdba541e59dc35aca2441c814.json"}}, {"family": "Tyers", "given": "Mike", "initials": "M"}, {"family": "Avizonis", "given": "Daina", "initials": "D"}, {"family": "Larsson", "given": "Ola", "initials": "O"}, {"family": "Postovit", "given": "Lynne-Marie", "initials": "LM", "orcid": "0000-0002-8088-4197", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/37b54e991a3f4cd79cafb136421b5ac0.json"}}, {"family": "Djuranovic", "given": "Sergej", "initials": "S", "orcid": "0000-0002-9417-0822", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/130f6ab03e1548bba42dd3b630b722be.json"}}, {"family": "Ursini-Siegel", "given": "Josie", "initials": "J"}, {"family": "Siegel", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-5568-6586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c593530a17f471a8f54f573996a4b5e.json"}}, {"family": "Pollak", "given": "Michael", "initials": "M", "orcid": "0000-0003-3047-0604", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/858cd217eb024fafaf5614050d6b9c33.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}], "type": "journal article", "published": "2026-05-05", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "14", "issn-l": "2050-084X"}, "abstract": "Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM6 cells, and its expression is reduced across human cancers. In various human cancer cell lines and mouse models, ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilisation but paradoxically increases bioenergetics and accelerates neoplastic growth via activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH downregulation leads to bioenergetic and signaling reprogramming that accelerates neoplastic growth.", "doi": "10.7554/eLife.106587", "pmid": "42085321", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC13143275"}, {"db": "pii", "key": "106587"}], "notes": [], "created": "2026-08-20T13:51:28.674Z", "modified": "2026-08-20T13:51:29.175Z"}, {"entity": "publication", "iuid": "2598dba6b2ec40e6a4e38faa37025e37", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2598dba6b2ec40e6a4e38faa37025e37.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2598dba6b2ec40e6a4e38faa37025e37"}}, "title": "Translon: a single term for translated regions.", "authors": [{"family": "\u015awirski", "given": "Micha\u0142 I", "initials": "MI", "orcid": "0000-0002-8585-136X", 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"https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Hatzoglou", "given": "Maria", "initials": "M", "orcid": "0000-0003-2037-1231", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbc5330f8c84c548a8472bb81cf77f3.json"}}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "641", "issue": "8065", "pages": "1319-1328", "issn-l": "0028-0836"}, "abstract": "An increased level of phosphorylation of eukaryotic translation initiation factor 2 subunit-\u03b1 (eIF2\u03b1, encoded by EIF2S1; eIF2\u03b1-p) coupled with decreased guanine nucleotide exchange activity of eIF2B is a hallmark of the 'canonical' integrated stress response (c-ISR)1. It is unclear whether impaired eIF2B activity in human diseases including leukodystrophies2, which occurs in the absence of eIF2\u03b1-p induction, is synonymous with the c-ISR. Here we describe a mechanism triggered by decreased eIF2B activity, distinct from the c-ISR, which we term the split ISR (s-ISR). The s-ISR is characterized by translational and transcriptional programs that are different from those observed in the c-ISR. Opposite to the c-ISR, the s-ISR requires eIF4E-dependent translation of the upstream open reading frame 1 and subsequent stabilization of ATF4 mRNA. This is followed by altered expression of a subset of metabolic genes (for example, PCK2), resulting in metabolic rewiring required to maintain cellular bioenergetics when eIF2B activity is attenuated. Overall, these data demonstrate a plasticity of the mammalian ISR, whereby the loss of eIF2B activity in the absence of eIF2\u03b1-p induction activates the eIF4E-ATF4-PCK2 axis to maintain energy homeostasis.", "doi": "10.1038/s41586-025-08794-6", "pmid": "40140574", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12119373"}, {"db": "pii", "key": "10.1038/s41586-025-08794-6"}], "notes": [], "created": "2026-08-20T08:59:09.414Z", "modified": "2026-08-20T08:59:10.076Z"}, {"entity": "publication", "iuid": "aa8fbfaa74e3412fbef4871d1c15f9df", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/aa8fbfaa74e3412fbef4871d1c15f9df.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/aa8fbfaa74e3412fbef4871d1c15f9df"}}, "title": "Guidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR).", "authors": [{"family": "Loughran", "given": "Gary", "initials": "G", "orcid": "0000-0002-2683-5597", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c311a8bb78647dbb1d9f4151c5e408b.json"}}, {"family": "Andreev", "given": "Dmitry E", "initials": "DE", "orcid": "0000-0001-5320-3045", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36a203947cc34c35af7fca9c277faff5.json"}}, {"family": "Terenin", "given": "Ilya M", "initials": "IM"}, {"family": "Namy", "given": "Olivier", "initials": "O", "orcid": "0000-0002-1143-5961", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5e5b761f20624e098e77f7a0819f73a1.json"}}, {"family": "Mikl", "given": "Martin", "initials": "M", "orcid": "0000-0001-8913-7158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b57ca06114054393a29ce7487f7da225.json"}}, {"family": "Yordanova", "given": "Martina M", "initials": "MM"}, {"family": "McManus", "given": "C Joel", "initials": "CJ", "orcid": "0000-0002-6605-2642", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1154f2331e5446aea6c28aeceeee3a21.json"}}, {"family": "Firth", "given": "Andrew E", "initials": "AE"}, {"family": "Atkins", "given": "John F", "initials": "JF", "orcid": "0000-0001-7933-0165", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d78917a7760f4b35a8bb8d781dea7c5f.json"}}, {"family": "Fraser", "given": "Christopher S", "initials": "CS", "orcid": "0000-0001-9626-7743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b7f1730af67400f9a838543d1e35fe9.json"}}, {"family": "Ignatova", "given": "Zoya", "initials": "Z", "orcid": "0000-0002-9478-8825", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9ff2bcc30ed4068a6c0b628f086a844.json"}}, {"family": "Iwasaki", "given": "Shintaro", "initials": "S", "orcid": "0000-0001-7724-3754", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f3f0fec7bb5a4a08bbd4b3b7c920444c.json"}}, {"family": "Kufel", "given": "Joanna", "initials": "J"}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Leidel", "given": "Sebastian A", "initials": "SA"}, {"family": "Mankin", "given": "Alexander S", "initials": "AS", "orcid": "0000-0002-3301-827X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51ec2601418a4be1aa88cd6fd0446e07.json"}}, {"family": "Mariotti", "given": "Marco", "initials": "M", "orcid": "0000-0002-7411-4161", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd21551aee634f42b1f8b2c9720e947d.json"}}, {"family": "Tanenbaum", "given": "Marvin E", "initials": "ME", "orcid": "0000-0001-8762-0090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab6de46d021a44558494cc2ce946b46e.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "V\u00e1zquez-Laslop", "given": "Nora", "initials": "N", "orcid": "0000-0003-2256-693X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e7993c94c0e4df68b0854c5b67d5167.json"}}, {"family": "Viero", "given": "Gabriela", "initials": "G"}, {"family": "Caliskan", "given": "Neva", "initials": "N", "orcid": "0000-0003-0435-4757", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7aef7adbfa9242abac425bb617fba4ae.json"}}, {"family": "Chen", "given": "Yiwen", "initials": "Y"}, {"family": "Clark", "given": "Patricia L", "initials": "PL", "orcid": "0000-0001-5462-8248", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/714cf357e7e84679be3c6c2ad18c6a3f.json"}}, {"family": "Dinman", "given": "Jonathan D", "initials": "JD", "orcid": "0000-0002-2402-9698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/947f8aa98d194d94bdb33b6f4fce1c30.json"}}, {"family": "Farabaugh", "given": "Philip J", "initials": "PJ", "orcid": "0000-0002-5658-7141", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1edad8fe5d4e47b9879788c3b934690f.json"}}, {"family": "Gilbert", "given": "Wendy V", "initials": "WV"}, {"family": "Ivanov", "given": "Pavel", "initials": "P", "orcid": "0000-0002-7986-7760", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/97e5a8913fa04346b59f6506352ada22.json"}}, {"family": "Kieft", "given": "Jeffrey S", "initials": "JS", "orcid": "0000-0002-3718-1891", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5e84a902110a4f78ba9c5871d54f5d6b.json"}}, {"family": "M\u00fchlemann", "given": "Oliver", "initials": "O"}, {"family": "Sachs", "given": "Matthew S", "initials": "MS", "orcid": "0000-0001-9891-9223", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e4116cf26f3b4f79b5c02f0f4402d438.json"}}, {"family": "Shatsky", "given": "Ivan N", "initials": "IN"}, {"family": "Sonenberg", "given": "Nahum", "initials": "N", "orcid": "0000-0002-4707-8759", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa0667a833e54844808bce0d4d00609d.json"}}, {"family": "Steckelberg", "given": "Anna-Lena", "initials": "AL"}, {"family": "Willis", "given": "Anne E", "initials": "AE", "orcid": "0000-0002-1470-8531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b11e8c4039c42b7bdc43cb6b7f4fa85.json"}}, {"family": "Woodside", "given": "Michael T", "initials": "MT"}, {"family": "Valasek", "given": "Leos Shivaya", "initials": "LS", "orcid": "0000-0001-8123-8667", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a73e4c57d07b45188685deb3fbe83043.json"}}, {"family": "Dmitriev", "given": "Sergey E", "initials": "SE", "orcid": "0000-0002-1774-8475", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c686d8d2507492b8eac91074e338593.json"}}, {"family": "Baranov", "given": "Pavel V", "initials": "PV", "orcid": "0000-0001-9017-0270", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9db030a647f4a72a9244d2052bbbd86.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Nat. Struct. Mol. Biol.", "issn": "1545-9985", "volume": "32", "issue": "3", "pages": "418-430", "issn-l": "1545-9985"}, "abstract": "Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. These effects may occur due to cryptic regulatory elements inducing or affecting transcription initiation, splicing, polyadenylation and antisense transcription as well as unpredictable effects of the translated test sequences on the stability and activity of the reporters. Unfortunately, these unintended effects may lead to misinterpretation of data and the publication of incorrect conclusions in the scientific literature. To address this issue and to assist the scientific community in accurately interpreting dual-reporter experiments, we have developed comprehensive guidelines. These guidelines cover experimental design, interpretation and the minimal requirements for reporting results. They are designed to aid researchers conducting these experiments as well as reviewers, editors and other investigators who seek to evaluate published data.", "doi": "10.1038/s41594-025-01492-x", "pmid": "40033152", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2090291"}, {"db": "pmc", "key": "PMC12246961"}, {"db": "pii", "key": "10.1038/s41594-025-01492-x"}], "notes": [], "created": "2026-08-20T09:03:55.131Z", "modified": "2026-08-20T09:03:55.608Z"}, {"entity": "publication", "iuid": "c28257475a734348b03f533c06754345", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c28257475a734348b03f533c06754345.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c28257475a734348b03f533c06754345"}}, "title": "SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.", "authors": [{"family": "Park", "given": "Juhyung", "initials": "J", "orcid": "0009-0008-6916-2784", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d6ef7bb356e410aa4219c27b08168e2.json"}}, {"family": "Wu", "given": "Jibo", "initials": "J"}, {"family": "Szkop", "given": "Krzysztof J", "initials": "KJ"}, {"family": "Jeong", "given": "Jinho", "initials": "J", "orcid": "0000-0002-1224-7196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbbe0377fe2b431cb698f1e0bd671776.json"}}, {"family": "Jovanovic", "given": "Predrag", "initials": "P", "orcid": "0000-0002-0090-0047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8084427ad2da44ba918b3cc9d77cf8f1.json"}}, {"family": "Husmann", "given": "Dylan", "initials": "D", "orcid": "0000-0003-1995-7892", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/da68a9ed090d49e1a79e83ed0f9ac49a.json"}}, {"family": "Flores", "given": "Natasha M", "initials": "NM"}, {"family": "Francis", "given": "Joel W", "initials": "JW"}, {"family": "Chen", "given": "Ying-Jiun C", "initials": "YC", "orcid": "0000-0002-6290-0771", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69277ae5a9474a08bc61176a010b39db.json"}}, {"family": "Benitez", "given": "Ana Morales", "initials": "AM", "orcid": "0000-0002-1021-5262", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5345b04beb854f1e9a3bb483bdf2143d.json"}}, {"family": "Zahn", "given": "Emily", "initials": "E"}, {"family": "Song", "given": "Shumei", "initials": "S", "orcid": "0000-0002-8128-6287", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0fb1a3e2dd3e4c608db294f5a977d97f.json"}}, {"family": "Ajani", "given": "Jaffer A", "initials": "JA", "orcid": "0000-0001-9946-0629", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13eb316de9424a65a37353d6341598be.json"}}, {"family": "Wang", "given": "Linghua", "initials": "L", "orcid": "0000-0001-9380-0266", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/366de0ac4cd74b6cbecc846bd466bae3.json"}}, {"family": "Singh", "given": "Kamini", "initials": "K"}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Garcia", "given": "Benjamin A", "initials": "BA", "orcid": "0000-0003-3596-4750", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3818fa278ebd4ab29155f78bd12ec54e.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Gozani", "given": "Or", "initials": "O", "orcid": "0000-0002-1365-4463", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb41c98a37274469a378ec1aee3c2e3a.json"}}, {"family": "Mazur", "given": "Pawel K", "initials": "PK", "orcid": "0000-0002-5820-8344", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dab982893e314975be2b45e274ee5d62.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "632", "issue": "8025", "pages": "656-663", "issn-l": "0028-0836"}, "abstract": "Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. 3) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in samples from patients with GAC and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease, including peritoneal carcinomatosis. Suppressing SMYD5 methylation of rpL40 inhibits human cancer cell and patient-derived GAC xenograft growth and renders them hypersensitive to inhibitors of PI3K and mTOR. Finally, combining SMYD5 depletion with PI3K-mTOR inhibition and chimeric antigen receptor T cell administration cures an otherwise lethal in vivo mouse model of aggressive GAC-derived peritoneal carcinomatosis. Together, our work uncovers a ribosome-based epigenetic mechanism that facilitates the evolution of malignant GAC and proposes SMYD5 targeting as part of a potential combination therapy to treat this cancer.", "doi": "10.1038/s41586-024-07718-0", "pmid": "39048817", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2037119"}, {"db": "pmc", "key": "PMC11625416"}, {"db": "pii", "key": "10.1038/s41586-024-07718-0"}], "notes": [], "created": "2026-08-20T08:58:56.543Z", "modified": "2026-08-20T08:58:57.111Z"}, {"entity": "publication", "iuid": "0562f7ae9ae74ce9be218b4602dcd4c7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0562f7ae9ae74ce9be218b4602dcd4c7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0562f7ae9ae74ce9be218b4602dcd4c7"}}, "title": "The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer.", "authors": [{"family": "Ghaddar", "given": "Nour", "initials": "N"}, {"family": "Wang", "given": "Shuo", "initials": "S"}, {"family": "Woodvine", "given": "Bethany", "initials": "B", "orcid": "0000-0001-8359-6476", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b06f2ec71304b0196962103c15aefe9.json"}}, {"family": "Krishnamoorthy", "given": "Jothilatha", "initials": "J"}, {"family": "van Hoef", "given": "Vincent", "initials": "V"}, {"family": "Darini", "given": "Cedric", "initials": "C"}, {"family": "Kazimierczak", "given": "Urszula", "initials": "U"}, {"family": "Ah-Son", "given": "Nicolas", "initials": "N"}, {"family": "Popper", "given": "Helmuth", "initials": "H", "orcid": "0000-0003-4970-1265", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c125771dd9d40b28c0ec1108a2efdb8.json"}}, {"family": "Johnson", "given": "Myriam", "initials": "M"}, {"family": "Officer", "given": "Leah", "initials": "L", "orcid": "0000-0002-3690-2386", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9244a991003b48c4a624ff9fc105c50c.json"}}, {"family": "Teod\u00f3sio", "given": "Ana", "initials": "A", "orcid": "0000-0002-1386-6730", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f87a35d99867490aaf8e1120130837a8.json"}}, {"family": "Broggini", "given": "Massimo", "initials": "M", "orcid": "0000-0002-8138-9358", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b1e8ef5869dd4419a5c540a3071e7217.json"}}, {"family": "Mann", "given": "Koren K", "initials": "KK"}, {"family": "Hatzoglou", "given": "Maria", "initials": "M", "orcid": "0000-0003-2037-1231", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbc5330f8c84c548a8472bb81cf77f3.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Le Quesne", "given": "John", "initials": "J", "orcid": "0000-0003-3552-7446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6bbfa845cda4379b505dbb0091edcf6.json"}}, {"family": "Koromilas", "given": "Antonis E", "initials": "AE", "orcid": "0000-0003-1972-0799", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7825afc7ac8942819083ce7c570b5508.json"}}], "type": "journal article", "published": "2021-07-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "4651", "issn-l": "2041-1723"}, "abstract": "The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2\u03b1), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2\u03b1 causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment.", "doi": "10.1038/s41467-021-24661-0", "pmid": "34330898", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8324901"}, {"db": "pii", "key": "10.1038/s41467-021-24661-0"}], "notes": [], "created": "2026-08-20T08:51:39.836Z", "modified": "2026-08-20T08:51:40.199Z"}, {"entity": "publication", "iuid": "4288addfa25a47f3884be39dc34c3e89", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4288addfa25a47f3884be39dc34c3e89.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4288addfa25a47f3884be39dc34c3e89"}}, "title": "Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR.", "authors": [{"family": "Kaspar", "given": "Sophie", "initials": "S", "orcid": "0000-0002-0844-6432", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0cdeeebe478446cd86b3ae0be238ac03.json"}}, {"family": "Oertlin", "given": "Christian", "initials": "C"}, {"family": "Szczepanowska", "given": "Karolina", "initials": "K", "orcid": "0000-0003-4689-2350", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4526c9fd1045408d99d9f081e4331d0d.json"}}, {"family": "Kukat", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-8610-0189", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99feea57ad6c43c5b243857e88977bc6.json"}}, {"family": "Senft", "given": "Katharina", "initials": "K", "orcid": "0000-0003-2294-6481", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b044634fdab9416eae21512d1d57a822.json"}}, {"family": "Lucas", "given": "Christina", "initials": "C", "orcid": "0000-0002-6575-3877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b3ace6f7382f4d27bce2152f8a114ed9.json"}}, {"family": "Brodesser", "given": "Susanne", "initials": "S", "orcid": "0000-0001-5631-0663", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9bb2fb66786b410d8e61f0cda2c435e5.json"}}, {"family": "Hatzoglou", "given": "Maria", "initials": "M", "orcid": "0000-0003-2037-1231", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fbc5330f8c84c548a8472bb81cf77f3.json"}}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Trifunovic", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-5472-3517", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bec355885e34065983da151480f5cfe.json"}}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "22", "issn-l": "2375-2548"}, "abstract": "In response to disturbed mitochondrial gene expression and protein synthesis, an adaptive transcriptional response sharing a signature of the integrated stress response (ISR) is activated. We report an intricate interplay between three transcription factors regulating the mitochondrial stress response: CHOP, C/EBP\u03b2, and ATF4. We show that CHOP acts as a rheostat that attenuates prolonged ISR, prevents unfavorable metabolic alterations, and postpones the onset of mitochondrial cardiomyopathy. Upon mitochondrial dysfunction, CHOP interaction with C/EBP\u03b2 is needed to adjust ATF4 levels, thus preventing overactivation of the ATF4-regulated transcriptional program. Failure of this interaction switches ISR from an acute to a chronic state, leading to early respiratory chain deficiency, energy crisis, and premature death. Therefore, contrary to its previously proposed role as a transcriptional activator of mitochondrial unfolded protein response, our results highlight a role of CHOP in the fine-tuning of mitochondrial ISR in mammals.", "doi": "10.1126/sciadv.abf0971", "pmid": "34039602", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8153728"}, {"db": "pii", "key": "7/22/eabf0971"}], "notes": [], "created": "2026-08-20T11:58:37.274Z", "modified": "2026-08-20T11:58:37.736Z"}, {"entity": "publication", "iuid": "bde1f8a7fd4c450da87ddcfdec3445bb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bde1f8a7fd4c450da87ddcfdec3445bb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bde1f8a7fd4c450da87ddcfdec3445bb"}}, "title": "SPANX Control of Lamin A/C Modulates Nuclear Architecture and Promotes Melanoma Growth.", "authors": [{"family": "Lazar", "given": "Ikrame", "initials": "I"}, {"family": "Fabre", "given": "Bertrand", "initials": "B"}, {"family": "Feng", "given": "Yongmei", "initials": "Y"}, {"family": "Khateb", "given": "Ali", "initials": "A"}, {"family": "Turko", "given": "Patrick", "initials": "P", "orcid": "0000-0003-3695-8264", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eaec13fbe64e41629f4bd1f1363c1cbf.json"}}, {"family": "Martinez Gomez", "given": "Julia M", "initials": "JM"}, {"family": "Frederick", "given": "Dennie T", "initials": "DT"}, {"family": "Levesque", "given": "Mitchell P", "initials": "MP"}, {"family": "Feld", "given": "Lea", "initials": "L"}, {"family": "Zhang", "given": "Gao", "initials": "G", "orcid": "0000-0001-8617-8886", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/190e9b7601de488bbb1aa0d987cb52b5.json"}}, {"family": "Zhang", "given": "Tongwu", "initials": "T", "orcid": "0000-0003-2124-2706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e98a573ff5094d7899a1ae45d27f1920.json"}}, {"family": "James", "given": "Brian", "initials": "B"}, {"family": "Shklover", "given": "Jeny", "initials": "J"}, {"family": "Avitan-Hersh", "given": "Emily", "initials": "E", "orcid": "0000-0002-2154-7609", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdfd1d7733524cbaad8fc28b4038a7db.json"}}, {"family": "Livneh", "given": "Ido", "initials": "I"}, {"family": "Scortegagna", "given": "Marzia", "initials": "M"}, {"family": "Brown", "given": "Kevin", "initials": "K"}, {"family": "Larsson", "given": "Ola", "initials": "O"}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Wolfenson", "given": "Haguy", "initials": "H", "orcid": "0000-0001-6892-7839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ba4f291cb83e47d8b539baa311f1b74a.json"}}, {"family": "Herlyn", "given": "Meenhard", "initials": "M"}, {"family": "Flaherty", "given": "Keith", "initials": "K"}, {"family": "Dummer", "given": "Reinhard", "initials": "R"}, {"family": "Ronai", "given": "Ze'ev A", "initials": "ZA"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Mol. Cancer Res.", "issn": "1557-3125", "volume": "18", "issue": "10", "pages": "1560-1573", "issn-l": "1541-7786"}, "abstract": "Mechanisms regulating nuclear organization control fundamental cellular processes, including the cell and chromatin organization. Their disorganization, including aberrant nuclear architecture, has been often implicated in cellular transformation. Here, we identify Lamin A, among proteins essential for nuclear architecture, as SPANX (sperm protein associated with the nucleus on the X chromosome), a cancer testis antigen previously linked to invasive tumor phenotypes, interacting protein in melanoma. SPANX interaction with Lamin A was mapped to the immunoglobulin fold-like domain, a region critical for Lamin A function, which is often mutated in laminopathies. SPANX downregulation in melanoma cell lines perturbed nuclear organization, decreased cell viability, and promoted senescence-associated phenotypes. Moreover, SPANX knockdown (KD) in melanoma cells promoted proliferation arrest, a phenotype mediated in part by IRF3/IL1A signaling. SPANX KD in melanoma cells also prompted the secretion of IL1A, which attenuated the proliferation of na\u00efve melanoma cells. Identification of SPANX as a nuclear architecture complex component provides an unexpected insight into the regulation of Lamin A and its importance in melanoma. IMPLICATIONS: SPANX, a testis protein, interacts with LMNA and controls nuclear architecture and melanoma growth.", "doi": "10.1158/1541-7786.MCR-20-0291", "pmid": "32571981", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1605968"}, {"db": "pmc", "key": "PMC7541784"}, {"db": "pii", "key": "1541-7786.MCR-20-0291"}], "notes": [], "created": "2026-08-20T12:14:17.407Z", "modified": "2026-08-20T12:14:17.666Z"}, {"entity": "publication", "iuid": "53807bfb3ae44f8e891b9e6b4d8840e3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/53807bfb3ae44f8e891b9e6b4d8840e3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/53807bfb3ae44f8e891b9e6b4d8840e3"}}, "title": "RITA requires eIF2\u03b1-dependent modulation of mRNA translation for its anti-cancer activity.", "authors": [{"family": "Ristau", "given": "Johannes", "initials": "J"}, {"family": "van Hoef", "given": "Vincent", "initials": "V"}, {"family": "Peuget", "given": "Sylvain", "initials": "S", "orcid": "0000-0002-3315-1935", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/511ecb3ab7d7478f87a1dfc6562a6f5e.json"}}, {"family": "Zhu", "given": "Jiawei", "initials": "J"}, {"family": "Guan", "given": "Bo-Jhih", "initials": "BJ"}, {"family": "Liang", "given": "Shuo", "initials": "S"}, {"family": "Hatzoglou", "given": "Maria", "initials": "M"}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Selivanova", "given": "Galina", "initials": "G"}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}], "type": "journal article", "published": "2019-11-07", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "10", "issue": "11", "pages": "845", "issn-l": "2041-4889"}, "abstract": "Tumor protein 53 (p53, encoded by the TP53 gene) is a key tumor suppressor regulating cell fates in response to internal and external stresses. As TP53 is mutated or silenced in a majority of tumors, reactivation of p53 by small molecules represents a promising strategy in cancer therapeutics. One such agent is RITA (reactivation of p53 and induction of tumor cell apoptosis), which restores p53 expression in cells with hyperactive HDM2 and induces apoptosis. Yet, mechanisms underlying the anticancer activity of RITA are incompletely understood. Here we show that RITA suppresses mRNA translation independently of p53 by inducing eIF2\u03b1 phosphorylation. Surprisingly, reactivation of p53 following RITA treatment is critically dependent on eIF2\u03b1 phosphorylation. Moreover, inhibition of eIF2\u03b1 phosphorylation attenuates pro-apoptotic and anti-neoplastic effects of RITA, while inducing phosphorylation of eIF2\u03b1 enhances the anticancer activity of RITA. Collectively, these findings demonstrate that the translational machinery plays a major role in determining the antineoplastic activity of RITA, and suggest that combining p53 activators and translation modulators may be beneficial.", "doi": "10.1038/s41419-019-2074-3", "pmid": "31699971", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6838152"}, {"db": "pii", "key": "10.1038/s41419-019-2074-3"}], "notes": [], "created": "2026-08-20T08:49:30.605Z", "modified": "2026-08-20T08:49:30.788Z"}, {"entity": "publication", "iuid": "6d1bb3e6bdf04887a099653d7f1e2bd1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6d1bb3e6bdf04887a099653d7f1e2bd1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6d1bb3e6bdf04887a099653d7f1e2bd1"}}, "title": "An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic reprogramming and mammary tumorigenesis.", "authors": [{"family": "Smith", "given": "Harvey W", "initials": "HW"}, {"family": "Hirukawa", "given": "Alison", "initials": "A"}, {"family": "Sanguin-Gendreau", "given": "Virginie", "initials": "V"}, {"family": "Nandi", "given": "Ipshita", "initials": "I"}, {"family": "Dufour", "given": "Catherine R", "initials": "CR"}, {"family": "Zuo", "given": "Dongmei", "initials": "D"}, {"family": "Tandoc", "given": "Kristofferson", "initials": "K"}, {"family": "Leibovitch", "given": "Matthew", "initials": "M"}, {"family": "Singh", "given": "Salendra", "initials": "S"}, {"family": "Rennhack", "given": "Jonathan P", "initials": "JP"}, {"family": "Swiatnicki", "given": "Matthew", "initials": "M"}, {"family": "Lavoie", "given": "Cynthia", "initials": "C"}, {"family": "Papavasiliou", "given": "Vasilios", "initials": "V"}, {"family": "Temps", "given": "Carolin", "initials": "C"}, {"family": "Carragher", "given": "Neil O", "initials": "NO"}, {"family": "Unciti-Broceta", "given": "Asier", "initials": "A", "orcid": "0000-0003-1029-2855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3c9f3d1ab5a46668c5c43091b065395.json"}}, {"family": "Savage", "given": "Paul", "initials": "P", "orcid": "0000-0003-2881-6717", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1d2227759734a1e84d16928f4c5c468.json"}}, {"family": "Basik", "given": "Mark", "initials": "M"}, {"family": "van Hoef", "given": "Vincent", "initials": "V"}, {"family": "Larsson", "given": "Ola", "initials": "O", "orcid": "0000-0003-1412-1308", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f81c6cbbe564d38bc78d1af5153d804.json"}}, {"family": "Cooper", "given": "Caroline L", "initials": "CL"}, {"family": "Vargas Calderon", "given": "Ana Cristina", "initials": "AC"}, {"family": "Beith", "given": "Jane", "initials": "J"}, {"family": "Millar", "given": "Ewan", "initials": "E"}, {"family": "Selinger", "given": "Christina", "initials": "C"}, {"family": "Gigu\u00e8re", "given": "Vincent", "initials": "V", "orcid": "0000-0001-9567-3694", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71ce97337546454fb49554814f160dc5.json"}}, {"family": "Park", "given": "Morag", "initials": "M"}, {"family": "Harris", "given": "Lyndsay N", "initials": "LN"}, {"family": "Varadan", "given": "Vinay", "initials": "V"}, {"family": "Andrechek", "given": "Eran R", "initials": "ER"}, {"family": "O'Toole", "given": "Sandra A", "initials": "SA"}, {"family": "Topisirovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-5510-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bca1813f34c4864940ac6593044a9cc.json"}}, {"family": "Muller", "given": "William J", "initials": "WJ"}], "type": "journal article", "published": "2019-07-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "10", "issue": "1", "pages": "2901", "issn-l": "2041-1723"}, "abstract": "Dysregulation of histone modifications promotes carcinogenesis by altering transcription. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the role of EZH2 in this setting is unclear due to the context-dependent functions of PRC2 and the heterogeneity of breast cancer. Moreover, the mechanisms underlying PRC2 overexpression in cancer are obscure. Here, using multiple models of breast cancer driven by the oncogene ErbB2, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 overexpression via control of mRNA translation. By stimulating mitochondrial ATP production, c-Src suppresses energy stress, permitting sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumourigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.", "doi": "10.1038/s41467-019-10681-4", "pmid": "31263101", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6603039"}, {"db": "pii", "key": "10.1038/s41467-019-10681-4"}], "notes": [], "created": "2026-08-20T08:50:40.813Z", "modified": "2026-08-20T08:50:40.987Z"}]}