TGF-β promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85α.

Hamidi A, Song J, Thakur N, Itoh S, Marcusson A, Bergh A, Heldin CH, Landström M

Sci Signal 10 (486) - [2017-07-04; online 2017-07-04]

Transforming growth factor-β (TGF-β) is a pluripotent cytokine that regulates cell fate and plasticity in normal tissues and tumors. The multifunctional cellular responses evoked by TGF-β are mediated by the canonical SMAD pathway and by noncanonical pathways, including mitogen-activated protein kinase (MAPK) pathways and the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (AKT) pathway. We found that TGF-β activated PI3K in a manner dependent on the activity of the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6). TRAF6 polyubiquitylated the PI3K regulatory subunit p85α and promoted the formation of a complex between the TGF-β type I receptor (TβRI) and p85α, which led to the activation of PI3K and AKT. Lys

Affiliated researcher

PubMed 28676490

DOI 10.1126/scisignal.aal4186

Crossref 10.1126/scisignal.aal4186

pii: 10/486/eaal4186

Publications 9.5.0