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RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1α and modulates brown fat cell metabolism.

The transcriptional coactivator PGC-1α is a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell. PGC-1α is a short-lived protein, and the molecular components that control PGC-1α turnover and their functional importance in energy metabolism are largely unknown. Here we performed a luciferase-based overexpression screen and identified a Ring-finger-containing protein, RNF34, as a specific E3 ubiquitin ligase for PGC-1α. RNF34 is a nuclear protein that interacts with and ubiquitinates PGC-1α to promote its turnover. Interestingly, RNF34 binds to the C-terminal half of PGC-1α and targets it for degradation independently of the previously identified N-terminal phosphodegron motif. In brown fat cells, knockdown of RNF34 increases the endogenous PGC-1α protein level, uncoupling protein 1 (UCP1) expression, and oxygen consumption, while the opposite effects are observed in brown fat cells ectopically expressing wild-type RNF34 but not in cells expressing the ligase activity-defective mutant. Moreover, cold exposure and β3-adrenergic receptor signaling, conditions that induce PGC-1α expression, suppress RNF34 expression in the brown fat cell, indicating a physiological relevance of this E3 ligase in thermogenesis. Our results reveal that RNF34 is a bona fide E3 ubiquitin ligase for PGC-1α and negatively regulates brown fat cell metabolism.

Pubmed ID: 22064484

Authors

  • Wei P
  • Pan D
  • Mao C
  • Wang YX

Journal

Molecular and cellular biology

Publication Data

January 28, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: R01DK076118

Mesh Terms

  • Adipocytes, Brown
  • Animals
  • COS Cells
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cells, Cultured
  • Cercopithecus aethiops
  • Cold Temperature
  • Energy Metabolism
  • F-Box Proteins
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • Protein Binding
  • Trans-Activators
  • Ubiquitin-Protein Ligases
  • Ubiquitination
  • Up-Regulation