Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators

Sunkara S. Rao, Caryn Chu, D. Stave Kohtz

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5259-5267
Number of pages9
JournalMolecular and Cellular Biology
Volume14
Issue number8
DOIs
StatePublished - Aug 1994

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