Interferon-γ impairs physiologic downregulation of cyclin-dependent kinase inhibitor, p27Kip1, during G1 phase progression in macrophages

Cell cycle progression of mouse macrophage cells was impaired by interferon-gamma (IFN-gamma), The blockage of G1/S transition was associated with diminution of cyclin-dependent kinase-2 (CDK2)-associated kinase activities. The expression of p21(Cip1) was not upregulated by IFN-gamma, Instead, the physiologic downregulation of p27(Kip1) necessary for normal cell cycle progression did not take place sufficiently in the presence of IFN-gamma. During normal cell cycle progression, the levels of p27(Kip1) were maximal at early G1 and then decreased gradually. In the presence of IFN-gamma, however, the levels of p27(Kip1) discontinued to decrease at a late mid G1 point and were consistently as high as, or higher than, levels observed there. The steady, relatively high-level attachment of p27(Kip1) to CDK2 contributed to the insufficient formation of active cyclin/CDK2, possibly deferring cells from entering S phase. (C) 1999 International Society for Published by Elsevier Science Inc.