Show simple item record

dc.contributor.authorWebster, Kenneth
dc.contributor.authorParish, Joanna L
dc.contributor.authorPandya, Maya
dc.contributor.authorStern, Peter L
dc.contributor.authorClarke, Anthony R
dc.contributor.authorGaston, Kevin
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.
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
refterms.dateFOA2020-09-18T12:54:54Z
html.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.


Files in this item

Thumbnail
Name:
87.full.pdf
Size:
284.3Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record