title: Functional modulation of AMP-activated protein kinase by cereblon.
abstract: 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.
authors.affiliation: School of Life Sciences and Cell Dynamics Research Center, Gwangju Institute Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors.forename: Kwang Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Sooyeon
authors.initials: S
authors.lastname: Jo
authors.forename: Hyunyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jongwon
authors.initials: J
authors.lastname: Lee
authors.forename: Chul-Seung
authors.initials: CS
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D049069:ATP-Dependent Proteases; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502543:CRBN protein, human; C503910:CRBN protein, rat; D002352:Carrier Proteins; C549921:Crbn protein, mouse; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D055372:AMP-Activated Protein Kinases; D010447:Peptide Hydrolases; D049069:ATP-Dependent Proteases