Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation.
In a yeast two-hybrid screen using the full-length Akt as bait, we found that prohibitin 2 (PHB2) specifically interacts with Akt. The C terminus of Akt (amino acids 413-480) and a central region of PHB2 (amino acids 120-232) are responsible for their mutual interaction. PHB2 acts as a transcriptional repressor in cells. PHB2 interacts with both MyoD and MEF2, and represses both MyoD- and MEF2-dependent gene transcription. Furthermore, binding of PHB2 to both MyoD and MEF2 significantly decreases upon myogenic differentiation. When stably expressed in C2C12 myogenic cells, PHB2 inhibits myogenin induction and phenotypic muscle differentiation. PHB2 was found to specifically recruit histone deacetylase 1, which is probably responsible for its repressive activity. Co-expression of Akt can partially reduce PHB2 binding to MyoD and relieve the repressive effect of PHB2 on myogenic reporters, which could be one of the mechanisms underlying Akt-mediated MyoD activation and accelerated muscle differentiation.
Sun
Luguo
L
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, China.
Liu
Lanying
L
Yang
Xiang-Jiao
XJ
Wu
Zhenguo
Z
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D000091402:Prohibitins; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D064326:MEF2 Transcription Factors; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; C000717331:PHB2 protein, human; C000717333:Phb2 protein, mouse; D000091402:Prohibitins; D012097:Repressor Proteins; D006655:Histone Deacetylases