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The p107 tumor suppressor induces stable E2F DNA binding to repress target promoters

Oncogene volume 20, pages 1882–1891 (2001)Cite this article

Abstract

E2F transcription factors are key players in the regulation of proliferation, apoptosis, and differentiation in mammalian cells. E2Fs are negatively regulated by members of the retinoblastoma protein family, Rb, p107 and p130. During adenovirus infection, viral proteins are expressed that displace Rb family members from E2Fs and recruit E2F complexes to viral and cellular promoter regions. This recruitment of E2F involves the induction of stable E2F binding to inverted E2F binding sites in the Ad E2a and cellular E2F-1 promoters and induces both viral and cellular gene expression. The cellular p107 tumor suppressor also displays such regulation of E2F DNA binding activity. p107 induces stable E2F-4/DP binding to inverted E2F binding sites in the Ad E2a and cellular E2F-1 promoters. The induction of E2F DNA binding by p107 minimally requires the sequences in p107 that mediate E2F interaction. The related tumor suppressor, p130, also effects this function. p107 levels increase substantially as cells progress through S phase. p107 induction of E2F DNA binding was observed primarily in S phase cells coincident with the increase in p107 protein levels. The results of promoter activity assays directly correlate the induction of E2F DNA binding by p107 with effective transcriptional repression. These results support a model in which p107 and p130 induce the stable binding of E2F complexes to promoters that drive expression of critical regulatory proteins such as E2F-1. Since p107 and p130 bind histone deacetylase complexes (HDACs) which repress promoter activity, p107-E2F and p130-E2F would stably recruit repressor complexes to effect efficient promoter repression.

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Acknowledgements

We thank our colleagues for many helpful discussions. This research was supported by Public Health Service grants CA28146 from the National Institutes of Health to P Hearing. RJ O'Connor and JE Schaley were supported by NIH Training Grant CA09176.

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  1. Robert J O'Connor

    Present address: InGenuity Systems, 2160 Gold St., PO Box 2199, Alviso, 95002, CA, USA

  2. Joel E Schaley

    Present address: The Burnham Institute, 10901 N. Torrey Pines Rd, La Jolla, CA, 92037, USA

Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology School of Medicine, State University of New York, Stony Brook, New York, 11794, NY, USA

    Robert J O'Connor, Joel E Schaley, Gia Feeney & Patrick Hearing

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O'Connor, R., Schaley, J., Feeney, G. et al. The p107 tumor suppressor induces stable E2F DNA binding to repress target promoters. Oncogene 20, 1882–1891 (2001). https://doi.org/10.1038/sj.onc.1204278

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