P21 (WAF1 CIP1/SDI1) IS ELEVATED THROUGH A P53-INDEPENDENT PATHWAY BYMIMOSINE/

Tumor suppressor p53 is a nuclear protein that is induced by DNA damag e and is involved in G(1) and G(2) phase control of the cell cycle. p2 1(WAF1/CIP1/SDI1) (p21), a cyclin-dependent kinase inhibitor, is a dow nstream target and effector of p53 to induce G(1) arrest. Mimosine is a potent reversible late G(1) phase blocker of the cell cycle. In this study, we showed that mimosine can increase both p21 mRNA and protein levels, indirectly inhibit cyclin E-associated kinase activity withou t affecting the cyclin E protein level, block human breast cancer cell s (21PT) in the late G(1) phase of the cell cycle, and induce a p53-in dependent pal pathway in these cells, These results support the possib ility of restoring a G(1) checkpoint by use of mimosine. They also sug gest that the mechanism of the effect of mimosine is complex and may h ave more than one target in the cell.