| First Author | Tamaru T | Year | 2015 |
| Journal | PLoS Biol | Volume | 13 |
| Issue | 11 | Pages | e1002293 |
| PubMed ID | 26562092 | Mgi Jnum | J:227468 |
| Mgi Id | MGI:5700567 | Doi | 10.1371/journal.pbio.1002293 |
| Citation | Tamaru T, et al. (2015) CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock. PLoS Biol 13(11):e1002293 |
| abstractText | 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 CK2beta to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2alpha. 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-CK2beta 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. |
