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Negative Regulation of Histone H1 Kinase Expression by Mimosine, a Plant Amino Acid¹

Department of Microbiology, University of Southern California, Los Angeles, California 90033-1054 [A. S.], and Department of Ophthalmology, University of California, San Diego, La Jolla, California 92093-0946 [S. T. F.]

² To whom requests for reprints should be addressed, at Department of Microbiology, University of Southern California, 2011 Zonal Ave., HMR-405, Los Angeles, CA 90033-1054.

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.

¹ Parts of this work were performed in the laboratory of James R. Feramisco (University of California, San Diego).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 3/26/93. Accepted 11/15/93.

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