The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86150
Title:
The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway.
Authors:
Webster, Kenneth; Parish, Joanna L; Pandya, Maya; Stern, Peter L; Clarke, Anthony R; Gaston, Kevin
Abstract:
The human papillomavirus (HPV) E2 protein regulates viral gene expression and is also required for viral replication. HPV-transformed cells often contain chromosomally integrated copies of the HPV genome in which the viral E2 gene is disrupted. We have shown previously that re-expression of the HPV 16 E2 protein in HPV 16-transformed cells results in cell death via apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by overexpression of the HPV 16 E6 protein, but is increased by overexpression of wild-type p53. We show that mutations that block the DNA binding activity of E2 do not impair the ability of this protein to induce apoptosis. In contrast, removal of both N-terminal domains from the E2 dimer completely blocks E2-induced cell death. Heterodimers formed between wild-type E2 and N-terminally deleted E2 proteins also fail to induce cell death. Our data suggest that neither the DNA binding activity of E2 nor other HPV proteins are required for the induction of apoptosis by E2 and that E2-induced cell death occurs via a p53-dependent pathway.
Affiliation:
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Citation:
The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway. 2000, 275 (1):87-94 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
7-Jan-2000
URI:
http://hdl.handle.net/10541/86150
DOI:
10.1074/jbc.275.1.87
PubMed ID:
10617590
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWebster, Kennethen
dc.contributor.authorParish, Joanna Len
dc.contributor.authorPandya, Mayaen
dc.contributor.authorStern, Peter Len
dc.contributor.authorClarke, Anthony Ren
dc.contributor.authorGaston, Kevinen
dc.date.accessioned2009-11-13T15:59:15Z-
dc.date.available2009-11-13T15:59:15Z-
dc.date.issued2000-01-07-
dc.identifier.citationThe human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway. 2000, 275 (1):87-94 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid10617590-
dc.identifier.doi10.1074/jbc.275.1.87-
dc.identifier.urihttp://hdl.handle.net/10541/86150-
dc.description.abstractThe human papillomavirus (HPV) E2 protein regulates viral gene expression and is also required for viral replication. HPV-transformed cells often contain chromosomally integrated copies of the HPV genome in which the viral E2 gene is disrupted. We have shown previously that re-expression of the HPV 16 E2 protein in HPV 16-transformed cells results in cell death via apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by overexpression of the HPV 16 E6 protein, but is increased by overexpression of wild-type p53. We show that mutations that block the DNA binding activity of E2 do not impair the ability of this protein to induce apoptosis. In contrast, removal of both N-terminal domains from the E2 dimer completely blocks E2-induced cell death. Heterodimers formed between wild-type E2 and N-terminally deleted E2 proteins also fail to induce cell death. Our data suggest that neither the DNA binding activity of E2 nor other HPV proteins are required for the induction of apoptosis by E2 and that E2-induced cell death occurs via a p53-dependent pathway.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCOS Cells-
dc.subject.meshCell Transformation, Viral-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshDimerization-
dc.subject.meshHela Cells-
dc.subject.meshHumans-
dc.subject.meshMutation-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomaviridae-
dc.subject.meshPeptide Fragments-
dc.subject.meshProtein Binding-
dc.subject.meshRecombinant Proteins-
dc.subject.meshTransfection-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleThe human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen

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