Cell Cycle Arrest

Abstract

We were pleased to see the three reports (1-3) and Research News article by Jean Marx (p. 963) in the 17 February issue that highlight the induction of the protein p21(WAF1) cyclin-dependent kinase (Cdk) inhibitor in myogenesis (1) and the high level of expression of p21(WAF1) in terminally differentiated tissues (2). These findings elegantly extend the findings published last fall in our papers "Induction of p21 (WAF1/CIP1) during differentiation" (4) and "Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53" (5). We had reported that multiple differentiation inducers caused immediate-early and sustained upregulation of p21 in many cell types through a p53-independent pathway. The report by Skapek et al. (3) demonstrating p21(WAF1) reversal of a cyclin DI-mediated differentiation block in muscle raises the hope that in some settings p21 (WAF1 )inducing agents may be anti-oncogenic. We would caution, however, that this strategy would be ineffective in settings in which p21(WAF1) induction is uncoupled from growth arrest. An example is our demonstration that deregulated c-myc expression is capable of uncoupling p21(WAF1) induction both from growth arrest and from differentiation (4).