USP11 augments TGFβ signaling by deubiquitylating ALK5

Mazin A. Al-Salihi, Lina Herhaus, Thomas Macartney, Gopal P. Sapkota (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    65 Citations (Scopus)

    Abstract

    The TGFß receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFß signals, negatively regulates the TGFß pathway by recruiting E3 ubiquitin ligases and targeting TGFß receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFß signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFß receptor (ALK5), resulting in enhanced TGFß-induced gene transcription. The deubiquitylase activity of USP11 is required to enhance TGFß-induced gene transcription. RNAi-mediated depletion of USP11 results in inhibition of TGFß-induced SMAD2/3 phosphorylation and TGFß-mediated transcriptional responses. Central to TGFß pathway signalling in early embryogenesis and carcinogenesis is TGFß-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFß-induced epithelial to mesenchymal transition.
    Original languageEnglish
    Article number120063
    JournalOpen Biology
    Volume2
    DOIs
    Publication statusPublished - 2012

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