In addition to responding to environmental entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control. Post-transcriptional regulation for the rhythmic gating of metabolic enzymes remains elusive. Here, we show that arginine biosynthesis and subsequent ureagenesis are collectively regulated by CLOCK (circadian locomotor output cycles kaput) in circadian rhythms. Facilitated by BMAL1 (brain and muscle Arnt-like protein), CLOCK directly acetylates K165 and K176 of argininosuccinate synthase (ASS1) to inactivate ASS1, which catalyzes the rate-limiting step of arginine biosynthesis. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. Furthermore, we also identified NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) as acetylation substrates of CLOCK. Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes.
Pubmed ID: 28985504 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsThis monoclonal targets beta Actin
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets ALDH1A1 (B-5)
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis unknown targets Lamin A+C
View all literature mentionsThis monoclonal targets Lysine, acetyl
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis monoclonal targets IMPDH2 antibody [EPR8364(B)]
View all literature mentions