E2F and histone deacetylase mediate transforming growth factor β repression of cdc25A during keratinocyte cell cycle arrest Journal Article
| Authors: | Iavarone, A.; Massagué, J. |
| Article Title: | E2F and histone deacetylase mediate transforming growth factor β repression of cdc25A during keratinocyte cell cycle arrest |
| Abstract: | cdc25A is a tyrosine phosphatase that activates G1 cyclin-dependent kinases (Cdk's). In human keratinocytes, cdc25A expression is down-regulated after the initial drop in Cdk activity caused by cell exposure to the antimitogenic cytokine transforming growth factor β (TGF-β) or removal of serum factors. Here we show that the TGF-β-inhibitory-response element in the cdc25A promoter maps to an E2F site at nucleotides -62 to -55 from the transcription start site. This site is not required for basal transcription in keratinocytes. We provide evidence that the cell cycle arrest program activated by TGF-β in human keratinocytes includes the generation of E2F4- p130 complexes that in association with histone deacetylase HDAC1 inhibit the activity of the cdc25A promoter from this repressor E2F site. This mechanism is part of a program that places keratinocytes in the quiescent state following the initial drop in Cdk activity caused by cell exposure to TGF- β. |
| Keywords: | controlled study; protein expression; human cell; dna-binding proteins; proteins; cell cycle protein; cell cycle proteins; cell cycle; gene expression; cell growth; transforming growth factor beta; cell line; down-regulation; enzyme activity; keratinocyte; transcription factors; nuclear proteins; molecular sequence data; transcription factor e2f; carrier proteins; phosphoproteins; base sequence; retinoblastoma protein; keratinocytes; histone deacetylases; retinoblastoma-like protein p107; retinoblastoma-like protein p130; histone deacetylase; dna, complementary; transcription factor dp1; protein-tyrosine-phosphatase; promoter regions (genetics); cdc25 phosphatase; e2f transcription factors; humans; human; priority journal; article; e2f4 transcription factor; e2f2 transcription factor |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 19 |
| Issue: | 1 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1999-01-01 |
| Start Page: | 916 |
| End Page: | 922 |
| Language: | English |
| PUBMED: | 9858615 |
| PROVIDER: | scopus |
| PMCID: | PMC83949 |
| DOI: | 10.1128/MCB.19.1.916 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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