Vogelstein, Lane and Levine 2000: surfing the p53 network
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.
Overview
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.
- p53 integrates signals from DNA damage, oncogene activation and hypoxia through MDM2, ARF and stress kinases.
- Its outputs include cell cycle arrest, apoptosis, DNA repair and anti-angiogenic genes.
- Most cancers disable the network, either by TP53 mutation or by altering upstream regulators such as MDM2 amplification or ARF loss.
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.
- A review from 2000; many network components and p53 isoforms were identified later.
- Concise by design, so it omits much mechanistic detail.
Similar pages
not linked directly; found by shared links- Key paperEl-Deiry 1993: WAF1, the gene through which p53 stops cell division
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Bert Vogelstein, Tumour suppressor gene, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
- TermLi-Fraumeni syndrome (germline TP53)
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, TP53-mutated (p53-abnormal), The p53 network (guardian of the genome), TP53.
- TermHallmark: evading growth suppressors
Shares Tumour suppressor gene, The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint, TP53.
- TreatmentEprenetapopt
Shares The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint, TP53.
- TermApoptosis
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint, TP53.
- TermCell cycle
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint, TP53.
- CompanyBulsara Bioworks
Shares p53 / RB / cell-cycle checkpoint, TP53.
- IdeaDegrade the damaged p53 protein rather than trying to repair it
Shares p53 / RB / cell-cycle checkpoint, TP53.