The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation.

ABSTRACT: The circadian timing system synchronizes cellular function by coordinating rhythmic transcription via a transcription-translational feedback loop. How the circadian system regulates gene expression at the translational level remains a mystery. Here, we show that the key circadian transcription factor BMAL1 associates with the translational machinery in the cytosol and promotes protein synthesis. The mTOR-effector kinase, ribosomal S6 protein kinase 1 (S6K1), an important regulator of translation, rhythmically phosphorylates BMAL1 at an evolutionarily conserved site. S6K1-mediated phosphorylation is critical for BMAL1 to both associate with the translational machinery and stimulate protein synthesis. Protein synthesis rates demonstrate circadian oscillations dependent on BMAL1. Thus, in add

SUBMITTER: Lipton JO 

PROVIDER: S-EPMC4447213 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature