TRAF6 promotes TGFβ-induced invasion and cell-cycle regulation via Lys63-linked polyubiquitination of Lys178 in TGFβ type I receptor

TRAF6 promotes TGFβ-induced invasion and cell-cycle regulation via Lys63-linked polyubiquitination of Lys178 in TGFβ type I receptor

Transforming growth factor β (TGFβ) can act either as a tumor promoter or a tumor suppressor in a context-dependent manner. High levels of TGFβ are found in prostate cancer tissues and correlate with poor patient prognosis. We recently identified a novel TGFβ-regulated signaling cascade in which TGFβ type I receptor (TβRI) is activated by the E3 ligase TNF-receptor-associated factor 6 (TRAF6) v...

TRAF6 promotes TGFb-induced invasion and cell-cycle regulation via Lys63-linked polyubiquitination of Lys178 in TGFb type I receptor

TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer

Transforming growth factor β (TGFβ) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGFβ binding to type II and type I serine/threonine kinase receptors (TβRII and TβRI) causes activation of different intracellular signaling pathways. TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6...

TGFβ activates PI3K-AKT signaling via TRAF6

Deregulation of the PI3K/AKT pathway has been reported in many types of cancer, including prostate cancer. As AKT regulates survival, metabolism, migration and therapy resistance in cancer cells, aberrant, high activity of AKT is involved in poor prognosis in cancer patients [1]. Transforming growth factor-β (TGFβ) family members are important for regulation of embryogenesis and tissue homeosta...

APPL proteins promote TGFβ-induced nuclear transport of the TGFβ type I receptor intracellular domain

The multifunctional cytokine transforming growth factor-β (TGFβ) is produced by several types of cancers, including prostate cancer, and promote tumour progression in autocrine and paracrine manners. In response to ligand binding, the TGFβ type I receptor (TβRI) activates Smad and non-Smad signalling pathways. The ubiquitin-ligase tumour necrosis factor receptor-associated factor 6 (TRAF6) was ...