Cereblon attenuates DNA damage-induced apoptosis by regulating the transcription-independent function of p53.

ABSTRACT: Cereblon (CRBN) is the substrate receptor of the cullin 4-RING E3 ligase complex and has been employed for targeted protein degradation in the treatment of cancers. However, its normal physiological functions and molecular mechanism in the regulation of DNA damage response are largely unknown. Here we find that CRBN plays a protective role against DNA damage-induced apoptosis in cell lines and primary cells. Mechanistic studies demonstrate that although CRBN does not affect the ubiquitination and degradation of the tumor suppressor p53, it directly interacts with p53 and therefore, suppresses the interaction between p53 and anti-apoptotic regulators Bcl-2 and Bcl-X_L. CRBN depletion enhances the interaction between p53 and Bcl-2/Bcl-X_L, reduces mitochondrial membrane p

SUBMITTER: Zhou L 

PROVIDER: S-EPMC6347596 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature