Cyclin E and cyclin A as candidates for the restriction point protein

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.