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 journalArticle

110 Citations (Scopus)

Abstract

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
Volume27
Issue number11
DOIs
StatePublished - Jun 4 2008

Fingerprint

AMP-Activated Protein Kinases
Brown Adipose Tissue
Ubiquitination
Down-Regulation
Tissue
Degradation
Energy Metabolism
Protein Stability
Protein Subunits
Fibroblasts
Nutrition
Ubiquitin
Adipocytes
Endoplasmic Reticulum
Catalytic Domain
Homeostasis
Up-Regulation
Obesity
Diet
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Medicine(all)

Cite this

Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. / Qi, Jingzong; Gong, Jingyi; Zhao, Tongjin; Zhao, Jie; Lam, Penny; Ye, Jing; Li, John Zhong; Wu, Jiawei; Zhou, Hai Meng; Li, Peng.

In: EMBO Journal, Vol. 27, No. 11, 04.06.2008, p. 1537-1548.

Research output: Contribution to journalArticle

Qi, J, Gong, J, Zhao, T, Zhao, J, Lam, P, Ye, J, Li, JZ, Wu, J, Zhou, HM & Li, P 2008, 'Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue', EMBO Journal, vol. 27, no. 11, pp. 1537-1548. https://doi.org/10.1038/emboj.2008.92
Qi, Jingzong ; Gong, Jingyi ; Zhao, Tongjin ; Zhao, Jie ; Lam, Penny ; Ye, Jing ; Li, John Zhong ; Wu, Jiawei ; Zhou, Hai Meng ; Li, Peng. / Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. In: EMBO Journal. 2008 ; Vol. 27, No. 11. pp. 1537-1548.
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