# Levine 1997: p53, the cellular gatekeeper for growth and division

Source: https://onco.cc/key-papers/paper-levine-p53-gatekeeper-cell-1997/  
OnCo record `paper-levine-p53-gatekeeper-cell-1997` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The classic account of how the p53 protein senses DNA damage and other stress and then stops a cell dividing or makes it die, and why losing p53, as about half of cancers do, removes a central safeguard against cancer.

## Summary

Levine's review described p53 as a transcription factor kept at low levels by MDM2 and stabilised by signals including DNA damage, hypoxia and oncogene activation. Activated p53 induces genes that arrest the cell cycle, chiefly p21, or trigger apoptosis, so that damaged cells are repaired or removed. The review explained how p53 mutation in roughly half of human cancers, inheritance of a mutant allele in Li-Fraumeni syndrome, and viral proteins that inactivate p53 all remove this checkpoint, and it set out the MDM2 feedback loop that later became a drug target.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Cell
- Year: 1997
- DOI: 10.1016/S0092-8674(00)81871-1
- Authors: Levine AJ.
- Findings: p53 is stabilised by DNA damage, hypoxia and oncogene activation and acts as a transcription factor.; Its main outputs are cell cycle arrest through p21 and apoptosis, removing damaged cells.; MDM2 binds and degrades p53 in a negative feedback loop; p53 is mutated in about half of human cancers and inherited mutation causes Li-Fraumeni syndrome.
- What it means: This review fixed the picture of p53 as the guardian of the genome that every textbook uses. It explains why TP53-mutant cancers are aggressive and hard to treat, why MDM2 inhibitors are being developed to reactivate wild-type p53, and why germline TP53 testing matters in families.
- Caveats: Written before the discovery of many p53 targets and of gain-of-function effects of mutant p53.; A review; specific mechanisms have been refined since.

## Sources

- Full text (DOI): https://doi.org/10.1016/S0092-8674(00)81871-1

## Connected records

- key papers: [El-Deiry 1993: WAF1, the gene through which p53 stops cell division](https://onco.cc/key-papers/paper-el-deiry-waf1-p21-cell-1993/), [Hollstein 1991: p53 mutations in human cancers](https://onco.cc/key-papers/paper-hollstein-p53-mutations-science-1991/), [Vogelstein, Lane and Levine 2000: surfing the p53 network](https://onco.cc/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/)
- targets: [MDM2](https://onco.cc/targets/mdm2/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [Apoptosis](https://onco.cc/terms/apoptosis/), [Cell cycle](https://onco.cc/terms/cell-cycle/), [Li-Fraumeni syndrome (germline TP53)](https://onco.cc/terms/li-fraumeni/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/), [Tumour suppressor gene](https://onco.cc/terms/tumour-suppressor-gene/)

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