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The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth
Author(s) -
Brehm Alexander,
Nielsen Søren J.,
Miska Eric A.,
McCance Dennis J.,
Reid Juliet L.,
Bannister Andrew J.,
Kouzarides Tony
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.9.2449
Subject(s) - hdac11 , histone deacetylase 5 , histone deacetylase , biology , sap30 , histone deacetylase 2 , zinc finger , hdac10 , hdac4 , microbiology and biotechnology , acetylation , cancer research , histone h4 , histone , biochemistry , transcription factor , dna , gene
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 Mi2β, 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 Mi2β 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.