Negative regulation of histone H1 kinase expression by mimosine, a plant amino acid.
The plant amino acid mimosine has been shown to reversibly arrest mammalian cells in late G1 phase of the cell cycle. However, the underlying molecular mechanisms of this block are not as yet understood. Here we show that mimosine prevents the serum-stimulated synthesis and activation of histone H1 kinase, a crucial regulator of cell cycle progression. The same effect is observed in logarithmically growing primary cells as well as transformed cells. Concomitantly, hyperphosphorylation of the retinoblastoma tumor suppressor gene product is partially inhibited. These effects are fully reversible, because removal of mimosine restores histone H1 kinase activity and the cells resume growth. Because the activity of histone H1 kinase has been shown to be absolutely required for cell cycle progression, it is conceivable that the cytostatic effect of mimosine is due to its negative effects on synthesis and activity of this enzyme.
Feldman
S T
ST
Department of Microbiology, University of Southern California, Los Angeles 90033-1054.
Schönthal
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A
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D008898:Mimosine / Q000494:pharmacology*; D010766:Phosphorylation; D006656:Protamine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000378:metabolism
D016213:Cyclins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D008898:Mimosine; D006656:Protamine Kinase; D016203:CDC2 Protein Kinase