Functional modulation of AMP-activated protein kinase by cereblon
pmid: 21232561
Functional modulation of AMP-activated protein kinase by cereblon
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.
- Gwangju Institute of Science and Technology Korea (Republic of)
DNA, Complementary, Ubiquitin-Protein Ligases, Nerve Tissue Proteins, AMP-Activated Protein Kinases, Cell Line, Mice, ATP-Dependent Proteases, Binding protein, Animals, Humans, Cereblon, Molecular Biology, Adaptor Proteins, Signal Transducing, Ubiquitin-Protein Ligase Complexes, Cell Biology, Rats, Enzyme Activation, Autosomal recessive nonsyndromic mental retardation, AMP-activated protein kinase α1, Gene Expression Regulation, Carrier Proteins, Peptide Hydrolases, Protein Binding
DNA, Complementary, Ubiquitin-Protein Ligases, Nerve Tissue Proteins, AMP-Activated Protein Kinases, Cell Line, Mice, ATP-Dependent Proteases, Binding protein, Animals, Humans, Cereblon, Molecular Biology, Adaptor Proteins, Signal Transducing, Ubiquitin-Protein Ligase Complexes, Cell Biology, Rats, Enzyme Activation, Autosomal recessive nonsyndromic mental retardation, AMP-activated protein kinase α1, Gene Expression Regulation, Carrier Proteins, Peptide Hydrolases, Protein Binding
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