USP11 augments TGFβ signalling by deubiquitylating ALK5. Issue 6 (June 2012)

• Record Type: Journal Article
• Authors: Al-Salihi, Mazin A.; Herhaus, Lina; Macartney, Thomas; Sapkota, Gopal P.
• Is Part Of: Open biology. Volume 2:Issue 6(2012)
• Publication Date: 2012-06
• Subjects: USP11 -- USP15 -- TGFβ -- ALK5 -- ubiquitin -- cancer; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.120063
• Languages: English
• ISSNs: 2046-2441

Abstract

Summary: The TGFβ receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFβ signals, negatively regulates the TGFβ pathway by recruiting E3 ubiquitin ligases and targeting TGFβ receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFβ signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFβ receptor (ALK5), resulting in enhanced TGFβ-induced gene transcription. The deubiquitylase activity of USP11 is required to enhance TGFβ-induced gene transcription. RNAi -mediated depletion of USP11 results in inhibition of TGFβ-induced SMAD2/3 phosphorylation and TGFβ-mediated transcriptional responses. Central to TGFβ pathway signalling in early embryogenesis and carcinogenesis is TGFβ-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFβ-induced epithelial to mesenchymal transition.