The viral oncogene human papillomavirus E7 deregulates transcriptional silencing by Brm-related gene 1 via molecular interactions
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- The viral oncogene human papillomavirus E7 deregulates transcriptional silencing by Brm-related gene 1 via molecular interactions
- Lee, Daeyoup; Lim, Chunghun; Seo, Taegun; Kwon, Hyockman; Min, Hyesu; Choe, Joonho
- RETINOBLASTOMA TUMOR-SUPPRESSOR; MAMMALIAN SWI/SNF COMPLEXES; CELL-CYCLE ARREST; C-FOS GENE; TYPE-16 E7; HISTONE ACETYLATION; SACCHAROMYCES-CEREVISIAE; TRANSFORMING ACTIVITY; MUTATIONAL ANALYSIS; HUMAN KERATINOCYTES
- Issue Date
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.50, pp.48842 - 48848
- 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.
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