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p53 and E2F-1 Cooperate to Mediate Apoptosis

The tumor-suppressor protein p53 appears to function at the G1phase of the cell cycle as a checkpoint in response to DNA damage. Mutations in the p53 gene lead to an increased rate of genomic instability and tumorigenesis. The E2F-1 transcription factor is a protein partner of the retinoblastoma-sus...

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Published in:Proceedings of the National Academy of Sciences - PNAS 1994-04, Vol.91 (9), p.3602-3606
Main Authors: Wu, Xiangwei, Levine, Arnold J.
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Levine, Arnold J.
description The tumor-suppressor protein p53 appears to function at the G1phase of the cell cycle as a checkpoint in response to DNA damage. Mutations in the p53 gene lead to an increased rate of genomic instability and tumorigenesis. The E2F-1 transcription factor is a protein partner of the retinoblastoma-susceptibility gene product, RB. E2F-1 appears to function as a positive regulator or signal for entry into S phase. To explore possible interactions of p53 and E2F-1 in the cell cycle, a human E2F-1 expression plasmid was introduced into a murine cell line containing a temperature-sensitive p53 allele which produces a p53 protein in the wild-type conformation at 32⚬C and the mutant form at 37.5⚬C. Coexpression of the wild-type p53 protein and E2F-1 in these cells resulted in a rapid loss of cell viability through a process of apoptosis. Thus, the cell cycle utilizes an interacting or communicative pathway between RB-E2F-1 and p53.
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source Open Access: PubMed Central; JSTOR Archival Journals and Primary Sources Collection
subjects Ageing, cell death
Apoptosis
Base Sequence
Biochemistry
Biological and medical sciences
Carrier Proteins
Cell cycle
Cell Cycle Proteins
Cell growth
Cell lines
Cell physiology
Cellular biology
Deoxyribonucleic acid
DNA
DNA-Binding Proteins - metabolism
E2F Transcription Factors
E2F1 Transcription Factor
Fundamental and applied biological sciences. Psychology
Gels
Genes
Interphase
Kidney cells
Molecular and cellular biology
Molecular Sequence Data
Oligodeoxyribonucleotides - chemistry
Proteins
Recombinant Proteins
Retinoblastoma-Binding Protein 1
Transcription Factor DP1
Transcription Factors - physiology
Transfection
Tumor Suppressor Protein p53 - physiology
Viability
title p53 and E2F-1 Cooperate to Mediate Apoptosis
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