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Journal Club
p21WAF1/CIP1 May Be a Tumor Suppressor After All
Andrei L. Gartel
volume 6 | issue 8
August 2007Pages: 1171 - 1172
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A cyclin-dependent kinase (CDK) inhibitor p21WAF1/CIP1 is a major target of p53 and a key mediator of p53-dependent cell cycle arrest after DNA-damage. p21 inhibits cell proliferation mainly by interfering with cyclinE/cdk2 activity. Originally p21 was considered as a tumor-suppressor because it inhibits proliferation and is regulated by tumor suppressor p53. And subsequently some tumor suppressor functions for p21 were found in p21/p18 double deficient or aging p21-null mice. p21 also protects mice against chemical carcinogens indicating that p21 may act as a tumor suppressor. In contrast, we and others suggested before that p21 may also act as oncogene because it often displays antiapoptotic activities. This concept was supported by results of De la Cueva et al. who showed that deletion of p21 from p53-deficient mice resulted in a substantially longer survival and significantly reduced number of thymic lymphomas that could be explained by higher apoptotic rate in these mice. However, two papers that were published recently (15, 16) challenged the view that apoptosis is necessary for tumor suppression and suggested that p21 may act as tumor suppressor in mice because of its ability to induce cell cycle arrest. In both cases authors used a p53 mouse mutant p53R172P (corresponding to human p53R175) that was deficient for apoptosis, but not for p21 activation and cell cycle arrest. Previously, G. Lozano group developed knock-in mice with p53R172P mutant (instead of p53) and they found that these mice have prolonged survival compared to p53-null mice. They crossed these mice onto a p21-null background and they found that loss of p21 completely abolished the cell cycle arrest function of p53R172P and accelerated onset of tumors in p53R172P+/+ p21-/- mice suggesting that p21 may act as a tumor suppressor, responsible for checkpoint control and preservation of chromosomal stability.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.