Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators.
Activation of muscle gene transcription in differentiating skeletal myoblasts requires their withdrawal from the cell cycle. The effects of ectopic cyclin expression on activation of muscle gene transcription by myogenic basic helix-loop-helix (bHLH) regulators were investigated. Ectopic expression of cyclin D1, but not cyclins A, B1, B2, C, D3, and E, inhibited transcriptional activation of muscle gene reporter constructs by myogenic bHLH regulators in a dose-dependent manner. Ectopic expression of cyclin D1 inhibited the activity of a myogenic bHLH regulator mutant lacking the basic region protein kinase C site, indicating that phosphorylation of this site is not relevant to the mechanism of inhibition. Analysis of cyclin D1 mutants revealed that the C-terminal acidic region was required for inhibition of myogenic bHLH regulator activity, whereas an intact N-terminal pRb binding motif was not essential. Together, these results implicate expression of cyclin D1 as a central determinant of a putatively novel mechanism that links positive control of cell cycle progression to negative regulation of genes expressed in differentiated myocytes.
Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029.
S S
SS
Rao
C
C
Chu
D S
DS
Kohtz
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009132:Muscles / Q000502:physiology*; D017570:MyoD Protein / Q000502:physiology*; D015513:Oncogene Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D016213:Cyclins; D017570:MyoD Protein; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; D011494:Protein Kinases; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases