Functional modulation of AMP-activated protein kinase by cereblon

• Published in: Biochimica et biophysica acta 2011-03, Vol.1813 (3), p.448-455
• Main Authors: Lee, Kwang Min, Jo, Sooyeon, Kim, Hyunyoung, Lee, Jongwon, Park, Chul-Seung
• Format: Article
• Language: English
• Subjects: AMP-activated protein kinase α1; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; ATP-Dependent Proteases; Autosomal recessive nonsyndromic mental retardation; Binding protein; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cereblon; DNA, Complementary - genetics; Enzyme Activation; Gene Expression Regulation; Humans; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; Protein Binding; Rats; Ubiquitin-Protein Ligase Complexes
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2011.01.005

Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo. ►Cereblon (CRBN) directly interacts with the AMP-activated protein kinase (AMPK) α1. ►Expression of CRBN reduces the phosphorylation of AMPK α1. ►AMPK α1 can be potently activated by suppressing endogenous CRBN.