Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Otobe, Yuta | - |
dc.contributor.author | Eui Min Jeong | - |
dc.contributor.author | Ito, Shunsuke | - |
dc.contributor.author | Shinohara, Yuta | - |
dc.contributor.author | Kurabayashi, Nobuhiro | - |
dc.contributor.author | Aiba, Atsu | - |
dc.contributor.author | Fukada, Yoshitaka | - |
dc.contributor.author | Jae Kyoung Kim | - |
dc.contributor.author | Yoshitane, Hikari | - |
dc.date.accessioned | 2024-12-12T07:36:36Z | - |
dc.date.available | 2024-12-12T07:36:36Z | - |
dc.date.created | 2024-06-10 | - |
dc.date.issued | 2024-06 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://pr.ibs.re.kr/handle/8788114/15829 | - |
dc.description.abstract | In mammals, CLOCK and BMAL1 proteins form a heterodimer that binds to E-box sequences and activates transcription of target genes, including Period (Per). Translated PER proteins then bind to the CLOCK-BMAL1 complex to inhibit its transcriptional activity. However, the molecular mechanism and the impact of this PER-dependent inhibition on the circadian clock oscillation remain elusive. We previously identified Ser38 and Ser42 in a DNA-binding domain of CLOCK as phosphorylation sites at the PER-dependent inhibition phase. In this study, knockout rescue experiments showed that nonphosphorylatable (Ala) mutations at these sites shortened circadian period, whereas their constitutive-phospho-mimetic (Asp) mutations completely abolished the circadian rhythms. Similarly, we found that nonphosphorylatable (Ala) and constitutive-phospho-mimetic (Glu) mutations at Ser78 in a DNA-binding domain of BMAL1 also shortened the circadian period and abolished the rhythms, respectively. The mathematical modeling predicted that these constitutive-phospho-mimetic mutations weaken the DNA binding of the CLOCK-BMAL1 complex and that the nonphosphorylatable mutations inhibit the PER-dependent displacement (reduction of DNA-binding ability) of the CLOCK-BMAL1 complex from DNA. Biochemical experiments supported the importance of these phosphorylation sites for displacement of the complex in the PER2-dependent inhibition. Our results provide direct evidence that phosphorylation of CLOCK-Ser38/Ser42 and BMAL1-Ser78 plays a crucial role in the PER-dependent inhibition and the determination of the circadian period. | - |
dc.language | 영어 | - |
dc.publisher | National Academy of Sciences | - |
dc.title | Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.wosid | 001243918100003 | - |
dc.identifier.scopusid | 2-s2.0-85194887397 | - |
dc.identifier.rimsid | 83223 | - |
dc.contributor.affiliatedAuthor | Eui Min Jeong | - |
dc.contributor.affiliatedAuthor | Jae Kyoung Kim | - |
dc.identifier.doi | 10.1073/pnas.2316858121 | - |
dc.identifier.bibliographicCitation | Proceedings of the National Academy of Sciences of the United States of America, v.121, no.23, pp.e2316858121 | - |
dc.relation.isPartOf | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.citation.title | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.citation.volume | 121 | - |
dc.citation.number | 23 | - |
dc.citation.startPage | e2316858121 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | CRISPR-Cas9 | - |
dc.subject.keywordAuthor | DNA binding | - |
dc.subject.keywordAuthor | mathematical modeling | - |
dc.subject.keywordAuthor | phosphorylation | - |
dc.subject.keywordAuthor | circadian rhythm | - |