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Disruption of repressive p130-DREAM complexes by human papillomavirus 16 E6/E7 oncoproteins is required for cell-cycle progression in cervical cancer cells
- Source :
- The Journal of general virology. 92(Pt 11)
- Publication Year :
- 2011
-
Abstract
- Human papillomaviruses (HPVs) with tropism for mucosal epithelia are the major aetiological factors in cervical cancer. Most cancers are associated with so-called high-risk HPV types, in particular HPV16, and constitutive expression of the HPV16 E6 and E7 oncoproteins is critical for malignant transformation in infected keratinocytes. E6 and E7 bind to and inactivate the cellular tumour suppressors p53 and Rb, respectively, thus delaying differentiation and inducing proliferation in suprabasal keratinocytes to enable HPV replication. One member of the Rb family, p130, appears to be a particularly important target for E7 in promoting S-phase entry. Recent evidence indicates that p130 regulates cell-cycle progression as part of a large protein complex termed DREAM. The composition of DREAM is cell cycle-regulated, associating with E2F4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study, we addressed whether p130–DREAM is disrupted in HPV16-transformed cervical cancer cells and whether this is a critical function for E6/E7. We found that p130–DREAM was greatly diminished in HPV16-transformed cervical carcinoma cells (CaSki and SiHa) compared with control cell lines; however, when E6/E7 expression was targeted by specific small hairpin RNAs, p130–DREAM was reformed and the cell cycle was arrested. We further demonstrated that the profound G1 arrest in E7-depleted CaSki cells was dependent on p130–DREAM reformation by also targeting the expression of the DREAM component Lin-54 and p130. The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130–DREAM complex.
- Subjects :
- Papillomavirus E7 Proteins
Cell
Biology
Malignant transformation
Virology
Cell Line, Tumor
medicine
Humans
DREAM complex
Transcription factor
E2F4
Cell Proliferation
Human papillomavirus 16
Cell growth
Cell Cycle
Epithelial Cells
Kv Channel-Interacting Proteins
Oncogene Proteins, Viral
Cell cycle
humanities
Repressor Proteins
medicine.anatomical_structure
Crk-Associated Substrate Protein
Cell culture
embryonic structures
Host-Pathogen Interactions
biological phenomena, cell phenomena, and immunity
Protein Multimerization
Subjects
Details
- ISSN :
- 14652099
- Volume :
- 92
- Issue :
- Pt 11
- Database :
- OpenAIRE
- Journal :
- The Journal of general virology
- Accession number :
- edsair.doi.dedup.....2dce1afd7062bdc74281a7a5bb0ac2d9