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Molecular and Cellular Biology, September 1998, p. 5609-5619, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Fos Family Members Induce Cell Cycle Entry by Activating Cyclin D1

Jennifer R. Brown,1,2 Elizabeth Nigh,1,2 Richard J. Lee,3 Hong Ye,1,2 Margaret A. Thompson,1,2 Frederic Saudou,1,2 Richard G. Pestell,3 and Michael E. Greenberg1,2,*

Division of Neuroscience, Children's Hospital,1 and Department of Neurobiology, Harvard Medical School,2 Boston, Massachusetts 02115, and The Albert Einstein College of Medicine Cancer Center, Department of Developmental and Molecular Biology and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 104613

Received 19 November 1997/Returned for modification 4 January 1998/Accepted 25 June 1998

Expression of the fos family of transcription factors is stimulated by growth factors that induce quiescent cells to reenter the cell cycle, but the cellular targets of the Fos family that regulate cell cycle reentry have not been identified. To address this issue, mice that lack two members of the fos family, c-fos and fosB, were derived. The fosB-/- c-fos-/- mice are similar in phenotype to c-fos-/- mice but are 30% smaller. This decrease in size is consistent with an abnormality in cell proliferation. Fibroblasts derived from fosB-/- c-fos-/- mice were found to have a defect in proliferation that results at least in part from a failure to induce cyclin D1 following serum-stimulated cell cycle reentry. Although definitive evidence that c-Fos and FosB directly induce cyclin D1 transcription will require further analysis, these findings raise the possibility that c-Fos and FosB are either direct or indirect transcriptional regulators of the cyclin D1 gene and may function as a critical link between serum stimulation and cell cycle progression.

* Corresponding author. Mailing address: Division of Neuroscience, Children's Hospital, Boston, MA 02115. Phone: (617) 355-8344. Fax: (617) 738-1542. E-mail: greenberg{at}a1.tch.harvard.edu.

Molecular and Cellular Biology, September 1998, p. 5609-5619, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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