p21WAF1/CIP1/SDI1 is elevated through a p53-independent pathway by mimosine.
Tumor suppressor p53 is a nuclear protein that is induced by DNA damage and is involved in G1 and G2 phase control of the cell cycle. p21WAF1/CIP1/SDI1 (p21), a cyclin-dependent kinase inhibitor, is a downstream target and effector of p53 to induce G1 arrest. Mimosine is a potent reversible late G1 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 without affecting the cyclin E protein level, block human breast cancer cells (21PT) in the late G1 phase of the cell cycle, and induce a p53-independent p21 pathway in these cells. These results support the possibility of restoring a G1 checkpoint by use of mimosine. They also suggest that the mechanism of the effect of mimosine is complex and may have more than one target in the cell.
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Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
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D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008898:Mimosine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008898:Mimosine