| First Author | Chini CC | Year | 2013 |
| Journal | Biochem J | Volume | 451 |
| Issue | 3 | Pages | 453-61 |
| PubMed ID | 23398316 | Mgi Jnum | J:198046 |
| Mgi Id | MGI:5495335 | Doi | 10.1042/BJ20121085 |
| Citation | Chini CC, et al. (2013) DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbalpha. Biochem J 451(3):453-61 |
| abstractText | The nuclear receptor Rev-erbalpha has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbalpha controls circadian oscillations of several clock genes and Rev-erbalpha protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbalpha stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbalpha. Rev-erbalpha and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbalpha repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbalpha protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbalpha protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbalpha protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbalpha and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbalpha and proposes that Rev-erbalpha could be involved in mediating some of the physiological effects of DBC1. |
