The hypertrophic response in C2C12 myoblasts recruits the G1 cell cycle machinery.
Hypertrophy occurs in postmitotic muscle as an adaptive response to various physiological and pathological stresses. Studies in vascular smooth muscle cells and primary cardiomyocytes suggest that angiotensin II-mediated hypertrophy activates signaling pathways associated with cell proliferation. Regulation of cyclin-dependent kinase (Cdk)-cyclin activities is essential to cell size control in lower eukaryotes, yet their role in the hypertrophic response in muscle is incompletely understood. We describe an in vitro model of hypertrophy in C2C12 skeletal myoblasts and demonstrate that induction of hypertrophy involves transient activation of Cdk4, subsequent phosphorylation of Rb, and release of HDAC1 from the Rb inhibitory complex. We also demonstrate that E2F-1 becomes transcriptionally active yet remains associated with Rb. We propose a model whereby partial inactivation of the Rb complex leads to derepression of a subset of E2F-1 targets necessary for cell growth without division during hypertrophy.
Hlaing
Myint
M
Cardiovascular Research Institute, University of California, San Francisco, California 94143-0130, USA.
Shen
Xun
X
Dazin
Paul
P
Bernstein
Harold S
HS
D000804:Angiotensin II / Q000494:pharmacology; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000032:analysis; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase; D006655:Histone Deacetylases / Q000378:metabolism; D006984:Hypertrophy; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000473:pathology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; C058992:Tagln protein, mouse; D014157:Transcription Factors; D000804:Angiotensin II; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D006655:Histone Deacetylases