FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.

Suryo Rahmanto A, Savov V, Brunner A, Bolin S, Weishaupt H, Malyukova A, Rosén G, Čančer M, Hutter S, Sundström A, Kawauchi D, Jones DT, Spruck C, Taylor MD, Cho YJ, Pfister SM, Kool M, Korshunov A, Swartling FJ, Sangfelt O

EMBO J. 35 (20) 2192-2212 [2016-10-17; online 2016-09-13]

SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCF

Affiliated researcher

PubMed 27625374

DOI 10.15252/embj.201693889

Crossref 10.15252/embj.201693889

pii: embj.201693889
pmc: PMC5069553