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Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells

Human papillomaviruses (HPV) 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 transf...

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Main Authors: Nor Rashid, N., Yusof, R., Watson, R.J.
Format: Article
Published: Society For General Microbiology 2011
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R Medicine
Online Access:http://eprints.um.edu.my/1952/
http://www.ncbi.nlm.nih.gov/pubmed/21813705
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spelling my.um.eprints.19522014-12-12T01:50:48Z http://eprints.um.edu.my/1952/ Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells Nor Rashid, N. Yusof, R. Watson, R.J. R Medicine Human papillomaviruses (HPV) 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 E2F-4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study we addressed if 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 to control cell lines; however, when E6/E7 expression was targeted with specific shRNAs, 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, Lin54 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. Society For General Microbiology 2011 Article PeerReviewed Nor Rashid, N. and Yusof, R. and Watson, R.J. (2011) Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells. The Journal of General Virology. ISSN 0022-1317 http://www.ncbi.nlm.nih.gov/pubmed/21813705 21813705
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Nor Rashid, N.
Yusof, R.
Watson, R.J.
Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
description Human papillomaviruses (HPV) 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 E2F-4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study we addressed if 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 to control cell lines; however, when E6/E7 expression was targeted with specific shRNAs, 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, Lin54 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.
format Article
author Nor Rashid, N.
Yusof, R.
Watson, R.J.
author_facet Nor Rashid, N.
Yusof, R.
Watson, R.J.
author_sort Nor Rashid, N.
title Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
title_short Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
title_full Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
title_fullStr Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
title_full_unstemmed Disruption of repressive p130/DREAM complexes by HPV16 E6/E7 oncoproteins is required for cell cycle progression in cervical cancer cells
title_sort disruption of repressive p130/dream complexes by hpv16 e6/e7 oncoproteins is required for cell cycle progression in cervical cancer cells
publisher Society For General Microbiology
publishDate 2011
url http://eprints.um.edu.my/1952/
http://www.ncbi.nlm.nih.gov/pubmed/21813705
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score 13.211869

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