| RRC ID |
81830
|
| Author |
Masuda S, Kurabayashi N, Nunokawa R, Otobe Y, Kozuka-Hata H, Oyama M, Shibata Y, Inoue JI, Koebis M, Aiba A, Yoshitane H, Fukada Y.
|
| Title |
TRAF7 determines circadian period through ubiquitination and degradation of DBP.
|
| Journal |
Commun Biol
|
| Abstract |
D-site binding protein, DBP, is a clock-controlled transcription factor and drives daily rhythms of physiological processes through the regulation of an array of genes harboring a DNA binding motif, D-box. DBP protein levels show a circadian oscillation with an extremely robust peak/trough ratio, but it is elusive how the temporal pattern is regulated by post-translational regulation. In this study, we show that DBP protein levels are down-regulated by the ubiquitin-proteasome pathway. Analysis using 19 dominant-negative forms of E2 enzymes have revealed that UBE2G1 and UBE2T mediate the degradation of DBP. A proteomic analysis of DBP-interacting proteins and database screening have identified Tumor necrosis factor Receptor-Associated Factor 7 (TRAF7), a RING-type E3 ligase, that forms a complex with UBE2G1 and/or UBE2T. Ubiquitination analysis have revealed that TRAF7 enhances K48-linked polyubiquitination of DBP in cultured cells. Overexpression of TRAF7 down-regulates DBP protein level, while knockdown of TRAF7 up-regulates DBP in cultured cells. Knockout of TRAF7 in NIH3T3 cells have revealed that TRAF7 mediates the time-of-the-day-dependent regulation of DBP levels. Furthermore, TRAF7 has a period-shortening effect on the cellular clock. Together, TRAF7 plays an important role in circadian clock oscillation through destabilization of DBP.
|
| Volume |
7(1)
|
| Pages |
1280
|
| Published |
2024-10-8
|
| DOI |
10.1038/s42003-024-07002-x
|
| PII |
10.1038/s42003-024-07002-x
|
| PMID |
39379486
|
| PMC |
PMC11461874
|
| MeSH |
Animals
Circadian Clocks / genetics
Circadian Rhythm* / genetics
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Humans
Mice
NIH 3T3 Cells
Proteolysis
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism
Ubiquitination*
|
| Resource |
| Human and Animal Cells |
NIH3T3-3-4(RCB1862) |
