The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth.

The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth. Research Abstract Details 

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The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth. Abstract Text:

Maurizio Bocchetta,Sandra Eliasz,Melissa Arakelian De Marco,Jennifer Rudzinski,Lei Zhang,Michele Carbone,Maurizio Bocchetta,Sandra Eliasz,Melissa Arakelian De Marco,Jennifer Rudzinski,Lei Zhang,Michele Carbone,

Inactivation of cellular p53 is a crucial step in carcinogenesis. Accordingly, p53 is inactivated in most human cancers by different mechanisms. In cells infected with DNA tumor viruses, p53 is bound to the viral tumor antigens (Tag). The current "dogma" views the Tag-p53 complexes as a way of sequestering and inactivating p53. Using primary human cells and SV40-transformed human cells, we show that in addition to inactivating p53 tumor suppressor activities, the Tag-p53 complex has growth stimulatory activities that are required for malignant cell growth. We found that in human cells, Tag-p53 complexes regulate transcription of the insulin-like growth factor I (IGF-I) gene by binding to the IGF-I promoter together with pRb and p300. Depletion of p53 leads to structural rearrangements of this multiprotein complex, resulting in IGF-I promoter transcriptional repression and growth arrest. Our data provide a novel mechanistic and biological interpretation of the p53-Tag complexes and of DNA tumor virus transformation in general. In the model we propose, p53 is not a passive inactive partner of Tag. Instead the p53-Tag complex promotes malignant cell growth through its ability to activate the IGF-I signaling pathway. [Cancer Res 2008;68(4):1022-9].

The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth. Publishing Authors By Initials

M Bocchetta,S Eliasz,MA De Marco,J Rudzinski,L Zhang,M Carbone,M Bocchetta,S Eliasz,MA De Marco,J Rudzinski,L Zhang,M Carbone,

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The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer research

VOLUME: 68

Page Numbers: 1022-9

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 15

MONTH: Feb

YEAR: 2008

The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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AFFILIATION: Department of Pathology and Oncology Institute, Loyola University Chicago, Cancer Center, Maywood, Illinois and Thoracic Oncology Program, Cancer Research Center of Hawaii, and Department of Pathology, University of Hawaii Medical School, Honolulu, Hawaii

Country: United States

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MEDLINETA: Cancer Res

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