Journal
PLOS BIOLOGY
Volume 13, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1002293
Keywords
-
Categories
Funding
- Japanese MEXT (Ministry of Education, Culture, Sports, Science and Technology) (KAKENHI) [23590283, 15K08217, 15K08217) and TO (KAKENHI
- 26220805]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [15H05488, 26670024, 15K08217, 23590283, 26220805, 26830074] Funding Source: KAKEN
Ask authors/readers for more resources
Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK23 to BMAL1 inhibits BMAL1 -Ser90 phosphorylation by CK2a. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK23 binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available