BRCA1 regulates transforming growth factor-β (TGF-β1) signaling through Gadd45a by enhancing the protein stability of Smad4.

ABSTRACT: BRCA1 is a well established tumor suppressor gene, which is involved in many cellular processes, including DNA damage repair, cell cycle control, apoptosis, as well as transcriptional control. In this work, we have found that BRCA1 is involved in regulating TGF-β1/Smad pathway. The loss of endogenous BRCA1 greatly attenuated TGF-β1-induced growth inhibition and cell cycle G1 arrest. BRCA1 greatly maintains stability of Smad4 protein, and the loss of BRCA1 results in Smad4 down-regulation, which is likely related to its downstream gene Gadd45a. Gadd45a is able to interact with β-Trcp1, a-F-box protein of SCF E3 ligase, and consequently suppresses the ubiquitin-degradation of Smad4 by SCF(β-trcp1), as reflected by the observations that the induction of Gadd45a substantially stabilizes Smad4

SUBMITTER: Li D 

PROVIDER: S-EPMC5528796 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature