Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2

M. Teresa Sáenz-Robles, Jennifer A. Markovics, Jean Leon Chong, Rene Opavsky, Robert H. Whitehead, Gustavo Leone, James M. Pipas

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)13191-13199
Number of pages9
JournalJournal of virology
Volume81
Issue number23
DOIs
StatePublished - Dec 1 2007

Fingerprint

Simian virus 40
Viral Tumor Antigens
Neoplasm Antigens
hyperplasia
Hyperplasia
antigens
neoplasms
Enterocytes
enterocytes
Retinoblastoma Protein
S Phase
E2F Transcription Factors
interphase
transcription (genetics)
proteins
mice
cultured cells
Cultured Cells
cell cycle
Cell Cycle

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Sáenz-Robles, M. T., Markovics, J. A., Chong, J. L., Opavsky, R., Whitehead, R. H., Leone, G., & Pipas, J. M. (2007). Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. Journal of virology, 81(23), 13191-13199. https://doi.org/10.1128/JVI.01658-07

Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. / Sáenz-Robles, M. Teresa; Markovics, Jennifer A.; Chong, Jean Leon; Opavsky, Rene; Whitehead, Robert H.; Leone, Gustavo; Pipas, James M.

In: Journal of virology, Vol. 81, No. 23, 01.12.2007, p. 13191-13199.

Research output: Contribution to journalArticle

Sáenz-Robles, MT, Markovics, JA, Chong, JL, Opavsky, R, Whitehead, RH, Leone, G & Pipas, JM 2007, 'Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2', Journal of virology, vol. 81, no. 23, pp. 13191-13199. https://doi.org/10.1128/JVI.01658-07
Sáenz-Robles MT, Markovics JA, Chong JL, Opavsky R, Whitehead RH, Leone G et al. Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. Journal of virology. 2007 Dec 1;81(23):13191-13199. https://doi.org/10.1128/JVI.01658-07
Sáenz-Robles, M. Teresa ; Markovics, Jennifer A. ; Chong, Jean Leon ; Opavsky, Rene ; Whitehead, Robert H. ; Leone, Gustavo ; Pipas, James M. / Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. In: Journal of virology. 2007 ; Vol. 81, No. 23. pp. 13191-13199.
@article{c767890e6b514e6fa5ef011f3575c008,
title = "Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2",
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.",
author = "S{\'a}enz-Robles, {M. Teresa} and Markovics, {Jennifer A.} and Chong, {Jean Leon} and Rene Opavsky and Whitehead, {Robert H.} and Gustavo Leone and Pipas, {James M.}",
year = "2007",
month = "12",
day = "1",
doi = "10.1128/JVI.01658-07",
language = "English (US)",
volume = "81",
pages = "13191--13199",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2

AU - Sáenz-Robles, M. Teresa

AU - Markovics, Jennifer A.

AU - Chong, Jean Leon

AU - Opavsky, Rene

AU - Whitehead, Robert H.

AU - Leone, Gustavo

AU - Pipas, James M.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=36348937368&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348937368&partnerID=8YFLogxK

U2 - 10.1128/JVI.01658-07

DO - 10.1128/JVI.01658-07

M3 - Article

VL - 81

SP - 13191

EP - 13199

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -