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

J Qi, J Gong, T Zhao, J Zhao, P Lam, J Ye, JZ Li… - The EMBO …, 2008 - embopress.org
J Qi, J Gong, T Zhao, J Zhao, P Lam, J Ye, JZ Li, J Wu, HM Zhou, P Li
The EMBO journal, 2008embopress.org
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 …
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.
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