The viral oncogene human papillomavirus E7 deregulates transcriptional silencing by Brm-related gene 1 via molecular interactions.
BRG-1, a component of the human SWI/SNF complex, either activates or represses cellular promoters by modulating chromatin structure via the formation of a multiple polypeptide complex. Human papillomavirus E7 binds and destabilizes pRb, resulting in the blockage of G(1) arrest in the cell cycle. We show here that the high-risk human papillomavirus E7 protein group binds BRG-1 and modulates repression of the c-fos promoter mediated by this protein. In addition, both wild-type and Rb binding-defective E7 proteins abolish flat cell formation by BRG-1 in SW13 cells, whereas E7 COOH-terminal mutants do not affect this process. BRG-1-triggered repression of the c-fos promoter is sensitive to trichostatin A. We further establish that BRG-1 contains an activation domain and a trichostatin A-sensitive repression domain. These results collectively suggest that the viral oncogene E7 targets both pRb and BRG-1 via protein-protein interactions, resulting in the deregulation of host cell cycle control.
Lee
Daeyoup
D
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Lim
Chunghun
C
Seo
Taegun
T
Kwon
Hyockman
H
Min
Hyesun
H
Choe
Joonho
J
D000595:Amino Acid Sequence; D002460:Cell Line; D004265:DNA Helicases; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; C084108:SMARCA4 protein, human; D004265:DNA Helicases