E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha.

ABSTRACT: The metazoan circadian clock mechanism involves cyclic transcriptional activation and repression by proteins whose degradation is highly regulated via the ubiquitin-proteasome pathway. The heme receptor Rev-erb alpha, a core negative component of the circadian network, controls circadian oscillation of several clock genes, including Bmal1 Rev-erb alpha protein degradation can be triggered by inhibitors of glycogen synthase kinase 3beta, such as lithium, and also by serum shock, which synchronizes circadian rhythms in cultured cells. Here we report that two E3 ligases, Arf-bp1 and Pam (Myc-bp2), are copurified with Rev-erb alpha and required for its ubiquitination. RNA-interference-mediated depletion of Arf-bp1 and Pam stabilizes the Rev-erb alpha protein and protects Rev-erb alpha from deg

SUBMITTER: Yin L 

PROVIDER: S-EPMC2895127 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature