Identification of the FHL2 transcriptional coactivator as a new functional target of the E7 oncoprotein of human papillomavirus type 16.
We identified the transcriptional coactivator FHL2 as a novel target of the human papillomavirus type 16 (HPV-16) E7 oncoprotein, which plays a major role in cell transformation. The interaction with FHL2 is abolished by mutations in conserved regions 1 and 2 and in the C-terminal zinc finger domain of E7, all required for its transforming potential. We found that E7 impairs the coactivator function of FHL2 on both beta-catenin/LCF-dependent and AP-1-dependent promoters. Thus, the interaction with HPV-16 E7 leads to a promoter-specific impairment of FHL2 function and this may contribute to cell transformation.
Campo-Fernández
Beatriz
B
Tyrolean Cancer Research Institute at the Medical University Innsbruck, 6020 Innsbruck, Austria.
Morandell
Dieter
D
Santer
Frédéric R
FR
Zwerschke
Werner
W
Jansen-Dürr
Pidder
P
D000818:Animals; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D018398:Homeodomain Proteins / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D014157:Transcription Factors / Q000378:metabolism*
C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16