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p19ARF links the tumour suppressor p53 to Ras
Open accessAbstract
Normal healthy cells possess safeguard mechanisms that sense oncogenic signals and trigger anti-tumorigenic responses that limit the proliferative potential of cells harbouring active oncogenes. In particular, expression of the Ras oncogene in normal primary cells causes a cell-cycle arrest that involves the activation of the tumoursuppressor protein p53 (ref. 2). It has recently been reported that the tumour-suppressor p19ARF can activate p53 (refs 3–5). Here we show that p19ARF in the mouse (the human homologue is called p14ARF) is essential for the activation of p53 in response to oncogenic Ras. These results, together with the finding that p19ARF does not mediate the activation of p53 by DNA damage, dissociate the activation of p53 into two pathways: one pathway is induced by DNA damage and is independent of p19ARF, whereas the other pathway is induced by oncogenic Ras and is dependent on p19ARF.
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Cited by
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
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Metadata
- Authors
- Palmero, I., Pantoja, C., & Serrano, M.
- Venue
- Nature
- Published
- 1998-09
- Volume
- 395
- Issue
- 6698
- Pages
- 125-126
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1531836615
- Cited by
- 615
- References
- 0
- FWCI
- 19.69
- Type
- journal article
- Language
- en
- Open access
- green
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