Overexpression of c-fos inhibits down-regulation of a cyclin-dependent kinase-2 inhibitor p27Kip1 in splenic B cells activated by surface Ig cross-linking.
Splenic B cells activated by surface Ig (sIg) cross-linking transiently express the c-fos gene within 0.5 h and then enter into S phase of the cell cycle within 48 h. To investigate a role of c-fos in cell cycle progression, we used splenic B cells from IFN-alphabeta-inducible c-fos transgenic mice (Mx-c-fos). In the absence of IFN, the cell cycle progression of Mx-c-fos B cells stimulated with anti-IgM Ab was similar to that in control B cells. The cell cycle was arrested in G1 phase when we added IFN to the culture within 12 h after anti-IgM Ab stimulation, suggesting that overexpression of c-fos until mid-G1 phase perturbs activation of the cell cycle regulatory machinery. In control B cells, cyclin E and cdk2 were induced within 24 to 48 h after stimulation, and this induction was accompanied by down-regulation of a cdk2 inhibitor p27Kip1. As a consequence of these activation processes, cdk2 kinase activity was induced in B cells in the late G1 phase. However, kinase activity was not detected in Mx-c-fos B cells, presumably because the down-regulation of p27 was perturbed. These data suggest that c-Fos can negatively control cell cycle regulatory machinery in sIg-stimulated B cells.
Kobayashi
K
K
Division of Developmental Genetics, Chiba University School of Medicine, Japan.
Phuchareon
J
J
Inada
K
K
Tomita
Y
Y
Koizumi
T
T
Hatano
M
M
Miyatake
S
S
Tokuhisa
T
T
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D004790:Enzyme Induction / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D016762:Genes, fos / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007372:Interferons / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D025521:Tumor Suppressor Proteins
D000888:Antibodies, Anti-Idiotypic; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D008869:Microtubule-Associated Proteins; D011947:Receptors, Antigen, B-Cell; D025521:Tumor Suppressor Proteins; C044203:anti-IgM; D050760:Cyclin-Dependent Kinase Inhibitor p27; D007372:Interferons; D018844:Cyclin-Dependent Kinases