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A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor β-induced cell-cycle arrest

By Gisela F. Claassen and Stephen R. Hann


c-Myc plays a vital role in cell-cycle progression. Deregulated expression of c-Myc can overcome cell-cycle arrest in order to promote cellular proliferation. Transforming growth factor β (TGFβ) treatment of immortalized human keratinocyte cells inhibits cell-cycle progression and is characterized by down-regulation of c-Myc followed by up-regulation of p21CIP1. A direct role of c-Myc in this pathway was demonstrated by the observation that ectopic expression of c-Myc overcame the cell-cycle block induced by TGFβ treatment. The induction of p21CIP1 transcription by TGFβ was blocked in human keratinocyte cells stably expressing c-Myc. Furthermore, overexpression of c-Myc in NIH 3T3 cells repressed the basal levels of p21CIP1 mRNA. Repression of p21CIP1 transcription by c-Myc occurred at the promoter level in a region near the start site of transcriptional initiation and was independent of histone deacetylase activity. These data suggest that the down-regulation of c-Myc after TGFβ signaling is important for subsequent regulation of p21CIP1 and cell-cycle inhibition. Thus, repression of the cell-cycle inhibitory gene p21CIP1 plays a role in c-Myc-dependent cell-cycle progression

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2000
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Provided by: PubMed Central
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