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Molecular and Cellular Biology, July 1999, p. 4695-4702, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Serum-Induced Expression of the cdc25A Gene by Relief of E2F-Mediated Repression

Xi Chen and Ron Prywes*

Department of Biological Sciences, Columbia University, New York, New York 10027

Received 20 November 1998/Returned for modification 15 January 1999/Accepted 21 April 1999

The cdc25A gene encodes a tyrosine phosphatase which activates cyclin-dependent kinase activity in the G1 phase of the cell cycle. cdc25A RNA levels are induced from 3 to 6 h after serum induction of serum-starved NIH 3T3 cells, suggesting that the cdc25A gene is a delayed-early gene. Analysis of cdc25A promoter constructs showed that the cdc25A promoter is sufficient for serum induction. Surprisingly for a gene expressed in early to mid-G1, serum induction of the promoter requires an E2F site at position -62 in the promoter. Deletion or point mutation of the E2F site resulted in activation of expression in serum-starved cells and no further induction by serum treatment. E2F factors were found to bind to the cdc25A E2F site along with the retinoblastoma protein (Rb) family members p130 and p107. A shift in mobility of the E2F-p107 complex in extracts of cells induced for 6 h correlated with induction of cdc25A expression. These results suggest that serum induction of cdc25A expression is mediated by inactivation of p107 or p130, both of which repress transcription when bound to the promoter through E2F.

* Corresponding author. Mailing address: Department of Biological Sciences, Columbia University, 1212 Amsterdam Ave., MC2420, New York, NY 10027. Phone: (212) 854-8281. Fax: (212) 854-7655. E-mail: mrp6{at}columbia.edu.

Molecular and Cellular Biology, July 1999, p. 4695-4702, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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