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Downregulation of AMP‐activated protein kinase by Cidea‐mediated ubiquitination and degradation in brown adipose tissue
Author(s) -
Qi Jingzong,
Gong Jingyi,
Zhao Tongjin,
Zhao Jie,
Lam Penny,
Ye Jing,
Li John Zhong,
Wu Jiawei,
Zhou HaiMeng,
Li Peng
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.92
Subject(s) - biology , downregulation and upregulation , ubiquitin , adipose tissue , degradation (telecommunications) , microbiology and biotechnology , protein kinase a , protein degradation , kinase , amp activated protein kinase , brown adipose tissue , biochemistry , gene , ampk , telecommunications , computer science
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.