Recent evidence shows that the transcription of unique copy genes is necessary for the transition of cells from the resting stage, or from mitosis, to the S phase of the cell cycle. Clearly, it is important to identify the mRNAs and proteins that control the transition of cells from a resting to a growing stage. Our approach to this problem is to identify by appropriate techniques the mRNAs that are made when quiescent cells are stimulated to proliferate by serum or by certain virally coded proteins. Although the ultimate goal is the identification of the genes controlling cell proliferation, a more modest but also more realistic objective is the identification of genes that are expressed when cells effect the G?0? to G?1? to S transition. Operationally, this means identifying mRNAs and proteins present in G?1?- and S-phase cells, but absent in G?0? cells. The use of temperature-sensitive mutants of the cell cycle that arrest in G?1? at the restrictive temperature and the ability of isolating mRNAs and of matching them against a properly made cDNA library made the search for these specific mRNAs feasible. In addition, we hope to investigate the possibility of inhibiting cellular proliferation by the microinjection into the mammalian cell nuclei of monoclonal antibodies specific against certain cellular and viral proteins that have been implicated in the control of cell proliferation. We have made considerable progress in the past 2 years. We have identified four cell division cycle genes that are preferentially expressed in the G?1? phase of the cell cycle. Three of these genes increase markedly, even when the G?1? specific ts mutants of the cell cycle are stimulated at the nonpermissive temperature, indicating that these genes are early genes involved in cell cycle progression. Some of these cell cycle genes are overexpressed in chronic and acute myeloid leukemias, and one of them (2A9) has been shown to induce cellular DNA synthesis when microinjected into quiescent cells. (N)
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