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rdf:type |
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lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0033684,
umls-concept:C0037083,
umls-concept:C0127400,
umls-concept:C0302592,
umls-concept:C0334227,
umls-concept:C0999806,
umls-concept:C1413357,
umls-concept:C1516044,
umls-concept:C1704675,
umls-concept:C1710082,
umls-concept:C1720947
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pubmed:issue |
1
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pubmed:dateCreated |
2011-1-24
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pubmed:abstractText |
Human papillomavirus (HPV) E2 gene disruption is one of the key features of HPV-induced cervical malignant transformation. Though it is thought to prevent progression of carcinogenesis, the pro-apoptotic function of E2 protein remains poorly understood. This study shows that expression of HPV16 E2 induces apoptosis both in HPV-positive and -negative cervical cancer cell lines and leads to hyperactivation of caspase-8 and caspase-3. Activation of these signaling factors is responsible for the observed sensitivity to apoptosis upon treatment with anti-Fas antibody or TNF-?. In addition, immunoprecipitation experiments clearly show an interaction between HPV16 E2 and c-FLIP, a key regulator of apoptotic cell death mediated by death receptor signaling. Moreover, c-FLIP and a caspase-8 inhibitor protect cells from HPV16 E2-mediated apoptosis. Overexpression of c-FLIP rescues cervical cancer cells from apoptosis induced by HPV16 E2 protein expression. The data suggest that HPV16 E2 abrogates the apoptosis-inhibitory function of c-FLIP and renders the cell hypersensitive to the Fas/FasL apoptotic signal even below threshold concentration. This suggests a novel mechanism for deregulation of cervical epithelial cell growth upon HPV-induced transformation, which is of great significance in developing therapeutic strategies for intervention of cervical carcinogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FAIM protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Death Domain,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/anti-Fas monoclonal antibody,
http://linkedlifedata.com/resource/pubmed/chemical/oncogene protein E2, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1573-675X
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pubmed:author |
pubmed-author:DeanA CAC,
pubmed-author:DengDongruiD,
pubmed-author:FangYongY,
pubmed-author:FuY PYP,
pubmed-author:GaoQingleiQ,
pubmed-author:HanLinfeiL,
pubmed-author:HanZhiqiangZ,
pubmed-author:LiKezhenK,
pubmed-author:LiYanY,
pubmed-author:LiaoShujieS,
pubmed-author:MengLiL,
pubmed-author:SkuyMM,
pubmed-author:VighB JBJ,
pubmed-author:WangShixuanS,
pubmed-author:XXX,
pubmed-author:ZhouJianfengJ
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pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
55-66
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pubmed:meshHeading |
pubmed-meshheading:20882347-Antibodies, Monoclonal,
pubmed-meshheading:20882347-Apoptosis,
pubmed-meshheading:20882347-Apoptosis Regulatory Proteins,
pubmed-meshheading:20882347-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:20882347-Caspase 3,
pubmed-meshheading:20882347-Caspase 8,
pubmed-meshheading:20882347-Cell Line, Tumor,
pubmed-meshheading:20882347-DNA-Binding Proteins,
pubmed-meshheading:20882347-Female,
pubmed-meshheading:20882347-Gene Expression,
pubmed-meshheading:20882347-Humans,
pubmed-meshheading:20882347-Oncogene Proteins, Viral,
pubmed-meshheading:20882347-Papillomaviridae,
pubmed-meshheading:20882347-Receptors, Death Domain,
pubmed-meshheading:20882347-Signal Transduction,
pubmed-meshheading:20882347-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:20882347-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20882347-Up-Regulation,
pubmed-meshheading:20882347-Uterine Cervical Neoplasms
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pubmed:year |
2011
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pubmed:articleTitle |
Triggering of death receptor apoptotic signaling by human papillomavirus 16 E2 protein in cervical cancer cell lines is mediated by interaction with c-FLIP.
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pubmed:affiliation |
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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