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  • The EMBO Journal (1999) 18, 2449 - 2458
  • doi:10.1093/emboj/18.9.2449

The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth

Alexander Brehm1,3, Søren J. Nielsen1,3, Eric A. Miska1,3, Dennis J. McCance1,2, Juliet L. Reid1, Andrew J. Bannister1 and Tony Kouzarides1

  1. Wellcome/CRC Institute for Developmental and Cancer Biology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
  2. Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA
  3. A.Brehm, S.J.Nielsen and E.A.Miska contributed equally to this work

Correspondence to:

Tony Kouzarides, E-mail: tk106@mole.bio.cam.ac.uk

Received 8 February 1999; Accepted 10 March 1999; Revised 10 March 1999

E7 is the main transforming protein of human papilloma virus type 16 (HPV16) which is implicated in the formation of cervical cancer. The transforming activity of E7 has been attributed to its interaction with the retinoblastoma (Rb) tumour suppressor. However, Rb binding is not sufficient for transformation by E7. Mutations within a zinc finger domain, which is dispensable for Rb binding, also abolish E7 transformation functions. Here we show that HPV16 E7 associates with histone deacetylase in vitro and in vivo, via its zinc finger domain. Using a genetic screen, we identify Mi2beta, a component of the recently identified NURD histone deacetylase complex, as a protein that binds directly to the E7 zinc finger. A zinc finger point mutant which is unable to bind Mi2beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells. Our results suggest that the binding to a histone deacetylase complex is an important parameter for the growthpromoting activity of the human papilloma virus E7 protein. This provides the first indication that viral oncoproteins control cell proliferation by targeting deacetylation pathways.

  • Keywords:

    • histone deacetylase,
    • human papilloma virus E7 oncoprotein,
    • Mi2,
    • transformation