p53 and E2F-1 Cooperate to Mediate Apoptosis

• 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.
• Format: Article
• Language: English
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.9.3602

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.