Interferon-gamma 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 p21Cip1 was not upregulated by IFN-gamma. Instead, the physiologic downregulation of p27Kip1 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 p27Kip1 were maximal at early G1 and then decreased gradually. In the presence of IFN-gamma, however, the levels of p27Kip1 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 p27Kip1 to CDK2 contributed to the insufficient formation of active cyclin/CDK2, possibly deferring cells from entering S phase.
Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
M
M
Matsuoka
I
I
Nishimoto
S
S
Asano
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007371:Interferon-gamma; D018844:Cyclin-Dependent Kinases