Regulation of the Product of a Possible Human Cell Cycle Control Gene CDC2Hs in B-cells by α-Interferon and Phorbol Ester

The product of the cell cycle control gene cdc2 is required in yeast for transition through both G1 and G2 control points of the cell cycle. The homologous protein in higher eukaryotes has been shown to be a component of the mitosis promoting factor complex and may thus regulate entry through the G2 control point into mitosis. It is suggested from the work presented here that, as in yeast, the human CDC2Hs gene product (p34CDC2Hs) may also play a role in cell cycle control in the G1(G0) phase of the cell cycle. Interferon-alpha inhibits the growth of the human B-cell line Daudi in the G1(G0) phase of the cell cycle and prevents cells from entering S-phase. Culturing the cells with interferon-alpha inhibits the phosphorylation of p34CDC2Hs and causes the down-regulation of CDC2Hs mRNA. Phorbol ester also inhibits the Daudi cell cycle in G1(G0) and causes the inhibition of p34CDC2Hs phosphorylation and a reduction of CDC2Hs mRNA. These studies provide insights into the process of growth control and the cytostatic mechanism of interferon-alpha.