Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue

Jingzong Qi, Jingyi Gong, Tongjin Zhao, Jie Zhao, Penny Lam, Jing Ye, John Zhong Li, Jiawei Wu, Hai Meng Zhou, Peng Li

Research output: Contribution to journalArticlepeer-review

132 Scopus citations


We previously showed that Cidea-/- mice are resistant to diet-induced obesity through the upregulation of energy expenditure. The AMP-activated protein kinase (AMPK), consisting of catalytic α subunit and regulatory subunits β and γ, has a pivotal function in energy homoeostasis. We show here that AMPK protein levels and enzymatic activity were significantly increased in the brown adipose tissue of Cidea-/- mice. We also found that Cidea is colocalized with AMPK in the endoplasmic reticulum and forms a complex with AMPK in vivo through specific interaction with the β subunit of AMPK, but not with the α or γ subunit. When co-expressed with Cidea, the stability of AMPK-β subunit was dramatically reduced due to increased ubiquitination-mediated degradation, which depends on a physical interaction between Cidea and AMPK. Furthermore, AMPK stability and enzymatic activity were increased in Cidea-/- adipocytes differentiated from mouse embryonic fibroblasts or preadipocytes. Our data strongly suggest that AMPK can be regulated by Cidea-mediated ubiquitin-dependent proteosome degradation, and provide a molecular explanation for the increased energy expenditure and lean phenotype in Cidea-null mice.

Original languageEnglish (US)
Pages (from-to)1537-1548
Number of pages12
JournalEMBO Journal
Issue number11
StatePublished - Jun 4 2008


  • AMPK
  • Brown adipose tissue
  • Cidea
  • Protein degradation
  • Ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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