Induction of DNA synthesis and apoptosis are separable functions of E2F-1.

TY - JOUR

T1 - Induction of DNA synthesis and apoptosis are separable functions of E2F-1.

AU - Phillips, A C

AU - Bates, S

AU - Ryan, K M

AU - Helin, K

AU - Vousden, K H

N1 - Keywords: Apoptosis; Carrier Proteins; Cell Cycle Proteins; Cell Line; Cyclins; DNA Replication; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Transcription Factors; Tumor Suppressor Protein p53

PY - 1997

Y1 - 1997

N2 - The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E2F-1, suggesting that it may be mediated through alleviation of E2F-dependent transcriptional repression. These results indicate that E2F-1 can show independent cell cycle progression and apoptotic functions, consistent with its putative role as a tumor suppressor.

AB - The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E2F-1, suggesting that it may be mediated through alleviation of E2F-dependent transcriptional repression. These results indicate that E2F-1 can show independent cell cycle progression and apoptotic functions, consistent with its putative role as a tumor suppressor.

M3 - Journal article

C2 - 9242492

SN - 0890-9369

VL - 11

SP - 1853

EP - 1863

JO - Genes & Development

JF - Genes & Development

IS - 14

ER -