PDZK1-interacting protein 1 (PDZK1IP1) traps Smad4 protein and suppresses transforming growth factor-β (TGF-β) signaling.

ABSTRACT: Transforming growth factor (TGF)-β signaling in humans is stringently regulated to prevent excessive TGF-β signaling. In tumors, TGF-β signaling can both negatively and positively regulate tumorigenesis dependent on tumor type, but the reason for these opposite effects is unclear. TGF-β signaling is mainly mediated via the Smad-dependent pathway, and herein we found that PDZK1-interacting protein 1 (PDZK1IP1) interacts with Smad4. PDZK1IP1 inhibited both the TGF-β and the bone morphogenetic protein (BMP) pathways without affecting receptor-regulated Smad (R-Smad) phosphorylation. Rather than targeting R-Smad phosphorylation, PDZK1IP1 could interfere with TGF-β- and BMP-induced R-Smad/Smad4 complex formation. Of note, PDZK1IP1 retained Smad4 in the cytoplasm of TGF-β-stimulated cells. To pi

SUBMITTER: Ikeno S 

PROVIDER: S-EPMC6442039 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature