# El-Deiry 1993: WAF1, the gene through which p53 stops cell division

Source: https://onco.cc/key-papers/paper-el-deiry-waf1-p21-cell-1993/  
OnCo record `paper-el-deiry-waf1-p21-cell-1993` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The discovery of p21, the gene p53 switches on to halt cell division, which explained for the first time how the most commonly mutated cancer gene actually stops damaged cells from growing.

## Summary

El-Deiry, Vogelstein and colleagues searched for genes activated by wild-type p53 and identified WAF1, now called CDKN1A or p21, whose expression was induced by wild-type but not mutant p53 in human cells. Introducing WAF1 into cancer cell lines suppressed their growth. Independently identified at the same time as an inhibitor of cyclin-dependent kinases, p21 turned out to be the link between p53 activation and arrest of the cell cycle at the G1 checkpoint.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Cell
- Year: 1993
- DOI: 10.1016/0092-8674(93)90500-P
- Authors: El-Deiry WS, Tokino T, Velculescu VE, et al.
- Findings: WAF1 (p21, CDKN1A) was identified as a gene induced by wild-type p53 and not by tumour-derived mutant p53.; Expression of WAF1 suppressed the growth of human tumour cell lines.; p21 was shown by parallel work to inhibit cyclin-dependent kinases, providing the mechanism for p53-mediated cell cycle arrest.
- What it means: This paper closed the loop between DNA damage, p53 and the cell cycle machinery. p21 is now a standard marker of p53 activity, part of how chemotherapy and radiotherapy stop cells dividing, and a component of the senescence response that CDK4/6 inhibitors exploit.
- Caveats: Cell line study; the in vivo roles of p21 in tumour suppression proved more complex.; p21 is also induced by p53-independent signals.

## Sources

- Full text (DOI): https://doi.org/10.1016/0092-8674(93)90500-P

## Connected records

- key papers: [Levine 1997: p53, the cellular gatekeeper for growth and division](https://onco.cc/key-papers/paper-levine-p53-gatekeeper-cell-1997/), [Sherr and Roberts 1999: CDK inhibitors as regulators of the G1 phase](https://onco.cc/key-papers/paper-sherr-roberts-cdk-inhibitors-genesdev-1999/)
- targets: [CDK4/6](https://onco.cc/targets/cdk4-6/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/)
- terms: [Cell cycle](https://onco.cc/terms/cell-cycle/), [Tumour suppressor gene](https://onco.cc/terms/tumour-suppressor-gene/)
- people: [Bert Vogelstein](https://onco.cc/people/bert-vogelstein/)

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