title: CaMK IV phosphorylates prohibitin 2 and regulates prohibitin 2-mediated repression of MEF2 transcription.
abstract: Prohibitin 2 (PHB2) is an evolutionarily conserved and ubiquitously expressed multifunctional protein which is present in various cellular compartments including the nucleus. However, mechanisms underlying various functions of PHB2 are not fully explored yet. Previously we showed that PHB2 interacts with Akt and inhibits muscle differentiation by repressing the transcriptional activity of both MyoD and MEF2. Here we show that Calcium/Calmodulin-dependent kinase IV (CaMK IV) specifically binds to the C terminus of PHB2 and phosphorylates PHB2 at serine 91. Ectopic expression of CaMK IV and PHB2 in C2C12 cells results effectively in decreased PHB2-mediated repression of MEF2-dependent gene expression. Conversely, PHB2 mutant (S91A) resistant to CaMK IV phosphorylation has less effective in relieving the inhibition of MEF2 transcription by PHB2. Our findings suggest that CaMK IV interacts with and regulates PHB2 through phosphorylation, which could be one of the mechanisms underlying the CaMK-mediated activation of MEF2.
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Luguo
authors.initials: L
authors.lastname: Sun
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Honglan
authors.initials: H
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Liyan
authors.initials: L
authors.lastname: Sui
authors.forename: Weimin
authors.initials: W
authors.lastname: Yin
authors.forename: Kewei
authors.initials: K
authors.lastname: Ma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D051379:Mice; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D010766:Phosphorylation; D000091402:Prohibitins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D018006:Myogenic Regulatory Factors; C000717333:Phb2 protein, mouse; D000091402:Prohibitins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4