P21(WAF1/CIP1) may be a tumor suppressor after all.
The cyclin-dependent kinase inhibitor p21WAF1/CIP1 was originally considered to be a tumor-suppressor because it was identified as a key mediator of p53-dependent cell cycle arrest. However, it has been suggested that p21 may also act as an oncogene because it often inhibits apoptosis. For example, deletion of p21 from p53-deficient mice resulted in longer survival and in a significantly reduced number of thymic lymphomas that was explained by higher apoptotic rates in these mice. However, recently it has been shown that a p53 mutant that had lost its ability to induce apoptosis, but retained its ability to induce p21 and cell cycle arrest, was able to suppress lymphomagenesis in different cancer models. Tumor suppression by this p53 mutant was modulated by p21, which induced senescence and preserved chromosomal stability. These data suggest that the ability of p21 to induce cell-cycle arrest may lead to tumor suppression in some types of cancer.
Gartel
Andrei L
AL
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612 USA, agartel@uic.edu
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000502:physiology*; D007938:Leukemia / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins