VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type I receptor degradation.

ABSTRACT: The transforming growth factor-β (TGF-β) family controls embryogenesis, stem cell differentiation, and tissue homeostasis. However, how post-translation modifications contribute to fine-tuning of TGF-β family signaling responses is not well understood. Inhibitory (I)-Smads can antagonize TGF-β/Smad signaling by recruiting Smurf E3 ubiquitin ligases to target the active TGF-β receptor for proteasomal degradation. A proteomic interaction screen identified Vpr binding protein (VprBP) as novel binding partner of Smad7. Mis-expression studies revealed that VprBP negatively controls Smad2 phosphorylation, Smad2-Smad4 interaction, as well as TGF-β target gene expression. VprBP was found to promote Smad7-Smurf1-TβRI complex formation and induce proteasomal degradation of TGF-β type I receptor (TβR

SUBMITTER: Li Y 

PROVIDER: S-EPMC7109606 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature