Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control

C Deng, P Zhang, JW Harper, SJ Elledge, P Leder - Cell, 1995 - Elsevier
C Deng, P Zhang, JW Harper, SJ Elledge, P Leder
Cell, 1995Elsevier
p21CIP11WAF1 is a CDK Inhibitor regulated by the tumor suppressor p53 and is
hypothesized to mediate G1 arrest. p53 has been suggested to derive anti-oncogenic
properties from this relationship. To test these notions, we created mice lacking
p21CIP1/WAF1. They develop normally and (unlike p53−/− mice) have not developed
spontaneous malignancies during 7 months of observation. Nonetheless, p21−/− embryonic
fibroblasts are significantly deficient in their ability to arrest in G1 In response to DNA …
p21CIP11WAF1 is a CDK Inhibitor regulated by the tumor suppressor p53 and is hypothesized to mediate G1 arrest. p53 has been suggested to derive anti-oncogenic properties from this relationship. To test these notions, we created mice lacking p21CIP1/WAF1. They develop normally and (unlike p53−/− mice) have not developed spontaneous malignancies during 7 months of observation. Nonetheless, p21−/− embryonic fibroblasts are significantly deficient in their ability to arrest in G1 In response to DNA damage and nucleotide pool perturbation. p21−/− cells also exhibit a significant growth alteration in vitro, achieving a saturation density as high as that observed In p53−/− cells. In contrast, other aspects of p53 function, such as thymocytic apoptosis and the mitotic spindle checkpoint, appear normal. These results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the antiapoptotic and the anti-oncogenic effects of p53 are more complex.
Elsevier