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Intestinal Hyperplasia Induced by Simian Virus 40 Large Tumor Antigen Requires E2F2
- Source :
- Journal of Virology. 81:13191-13199
- Publication Year :
- 2007
- Publisher :
- American Society for Microbiology, 2007.
-
Abstract
- The simian virus 40 large T antigen contributes to neoplastic transformation, in part, by targeting the Rb family of tumor suppressors. There are three known Rb proteins, pRb, p130, and p107, all of which block the cell cycle by preventing the transcription of genes regulated by the E2F family of transcription factors. T antigen interacts directly with Rb proteins and disrupts Rb-E2F complexes both in vitro and in cultured cells. Consequently, T antigen is thought to inhibit transcriptional repression by the Rb family proteins by disrupting their interaction with E2F proteins, thus allowing E2F-dependent transcription and the expression of cellular genes needed for entry into S phase. This model predicts that active E2F-dependent transcription is required for T-antigen-induced transformation. To test this hypothesis, we have examined the status of Rb-E2F complexes in murine enterocytes. Previous studies have shown that T antigen drives enterocytes into S phase, resulting in intestinal hyperplasia, and that the induction of enterocyte proliferation requires T-antigen binding to Rb proteins. In this paper, we show that normal growth-arrested enterocytes contain p130-E2F4 complexes and that T-antigen expression destroys these complexes, most likely by stimulating p130 degradation. Furthermore, unlike their normal counterparts, enterocytes expressing T antigen contain abundant levels of E2F2 and E2F3a. Concomitantly, T-antigen-induced intestinal proliferation is reduced in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacking E2F1. These studies support a model in which T antigen eliminates Rb-E2F repressive complexes so that specific activator E2Fs can drive S-phase entry.
- Subjects :
- Gastrointestinal Diseases
Antigens, Polyomavirus Transforming
Immunology
Mice, Transgenic
E2F4 Transcription Factor
Simian virus 40
Biology
Microbiology
Transformation and Oncogenesis
Mice
E2F2 Transcription Factor
Antigen
Virology
Animals
E2F1
Neoplastic transformation
Transcription factor
E2F2
Mice, Knockout
Hyperplasia
Retinoblastoma-Like Protein p130
Activator (genetics)
Cell cycle
Cell biology
Enterocytes
Insect Science
biological phenomena, cell phenomena, and immunity
E2F Transcription Factors
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....aa3ff3be60ba4f3ca98565e53e537140