NEGATIVE REGULATION OF HISTONE-H1 KINASE EXPRESSION BY MIMOSINE, A PLANT AMINO-ACID

The plant amino acid mimosine has been shown to reversibly arrest mamm alian cells in late G1 phase of the cell cycle. However, the underlyin g molecular mechanisms of this block are not as yet understood. Here w e show that mimosine prevents the serum-stimulated synthesis and activ ation of histone H1 kinase, a crucial regulator of cell cycle progress ion. The same effect is observed in logarithmically growing primary ce lls as weil as transformed cells. Concomitantly, hyperphosphorylation of the retinoblastoma tumor suppressor gene product is partially inhib ited. These effects are fully reversible, because removal of mimosine restores histone H1 kinase activity and the cells resume growth. Becau se the activity of histone H1 kinase has been shown to be absolutely r equired for cell cycle progression, it is conceivable that the cytosta tic effect of mimosine is due to its negative effects on synthesis and activity of this enzyme.