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A concise map of the p53 system as a network: the stresses that activate it, the many genes it controls, and the feedback loops that keep it in check, explaining why a single gene sits at the centre of so much of cancer biology.
Written by three of the field's founders, this review presented p53 as a signalling network rather than a single switch. Upstream, DNA damage, oncogene activation, hypoxia and nucleotide depletion converge on p53 through kinases and the MDM2 and ARF regulators; downstream, p53 activates genes for cell cycle arrest, apoptosis, DNA repair and inhibition of angiogenesis. The authors emphasised the MDM2 negative feedback loop, the effects of viral oncoproteins and the fact that most cancers disable the network at one point or another, whether by mutating p53 itself or by altering its regulators.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, Bert Vogelstein, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares Tumour suppressor gene, The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint, TP53.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint, TP53.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint, TP53.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, TP53-mutated (p53-abnormal), The p53 network (guardian of the genome), TP53.
Shares The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint, TP53.
Shares Is aneuploidy itself a druggable vulnerability?, p53 / RB / cell-cycle checkpoint, TP53.
Shares Bert Vogelstein, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, TP53.