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Cyclin E and Cyclin A as Canadidates for the Restriction Point Protein¹

Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

Progression of cells into S phase is proposed to be determined by accumulation of a labile protein (the restriction point protein R; A. B. Pardee, Proc. Natl. Acad. Sci. USA, 71: 1286–1290, 1974). We report here that cyclin E and cyclin A proteins as well as their dependent histone H1 kinases satisfy all of the criteria for the R protein, which includes late G₁ phase increase, an excess delay of appearance after inhibition of protein synthesis in nontransformed cells, and a faster recovery in transformed cells. We suggest that the molecular basis of the R protein could be cyclin production and inactivation.

¹ Supported by USPHS Grants CA22427 and GM24571 (to A. B. P.) and by Biomedical Research Support Grant 2 S07RR05526-28 and a Barr Program Small Grant (to Q-P. D.).

² To whom requests for reprints should be addressed, at Division of Cell Growth and Regulation, Room D814, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 2/ 1/93. Accepted 2/16/93.

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