DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα

Claudia C.S. Chini, Carlos Escande, Veronica Nin, Eduardo N. Chini

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα 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 Reverbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Reverbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends onboth 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-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.

Original languageEnglish (US)
Pages (from-to)453-461
Number of pages9
JournalBiochemical Journal
Volume451
Issue number3
DOIs
StatePublished - May 1 2013

Keywords

  • BMAL1
  • Circadian
  • Deleted in Breast Cancer 1 (DBC1)
  • Protein stability
  • Rev-erbα

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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