The Journal of Immunology, Vol 158, Issue 5 2050-2056, Copyright © 1997 by American Association of Immunologists

ARTICLES

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

K Kobayashi, J Phuchareon, K Inada, Y Tomita, T Koizumi, M Hatano, S Miyatake and T Tokuhisa
Division of Developmental Genetics, Chiba University School of Medicine, Japan.

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.

This article has been cited by other articles:

				D. J. J. de Gorter, J. C. M. Vos, S. T. Pals, and M. Spaargaren The B Cell Antigen Receptor Controls AP-1 and NFAT Activity through Ras-Mediated Activation of Ral J. Immunol., February 1, 2007; 178(3): 1405 - 1414. [Abstract] [Full Text] [PDF]

				Y. Ohkubo, M. Arima, E. Arguni, S. Okada, K. Yamashita, S. Asari, S. Obata, A. Sakamoto, M. Hatano, J. O-Wang, et al. A Role for c-fos/Activator Protein 1 in B Lymphocyte Terminal Differentiation J. Immunol., June 15, 2005; 174(12): 7703 - 7710. [Abstract] [Full Text] [PDF]

				A. Sunters, D. P. Thomas, W. A. Yeudall, and A. E. Grigoriadis Accelerated Cell Cycle Progression in Osteoblasts Overexpressing the c-fos Proto-oncogene: INDUCTION OF CYCLIN A AND ENHANCED CDK2 ACTIVITY J. Biol. Chem., March 12, 2004; 279(11): 9882 - 9891. [Abstract] [Full Text] [PDF]

				F. H. Vasanwala, S. Kusam, L. M. Toney, and A. L. Dent Repression of AP-1 Function: A Mechanism for the Regulation of Blimp-1 Expression and B Lymphocyte Differentiation by the B Cell Lymphoma-6 Protooncogene J. Immunol., August 15, 2002; 169(4): 1922 - 1929. [Abstract] [Full Text] [PDF]

				S Kojima, M Hatano, S Okada, T Fukuda, Y Toyama, S Yuasa, H Ito, and T Tokuhisa Testicular germ cell apoptosis in Bcl6-deficient mice Development, January 1, 2001; 128(1): 57 - 65. [Abstract] [PDF]

				K. Kobayashi, M. Hatano, M. Otaki, T. Ogasawara, and T. Tokuhisa Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation PNAS, February 16, 1999; 96(4): 1457 - 1462. [Abstract] [Full Text] [PDF]

				S. Okada, T. Fukuda, K. Inada, and T. Tokuhisa Prolonged Expression of c-fos Suppresses Cell Cycle Entry of Dormant Hematopoietic Stem Cells Blood, February 1, 1999; 93(3): 816 - 825. [Abstract] [Full Text] [PDF]

				K. Inada, S. Okada, J. Phuchareon, M. Hatano, T. Sugimoto, H. Moriya, and T. Tokuhisa c-Fos Induces Apoptosis in Germinal Center B Cells J. Immunol., October 15, 1998; 161(8): 3853 - 3861. [Abstract] [Full Text] [PDF]

				M. H. Kaplan, C. Daniel, U. Schindler, and M. J. Grusby Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression Mol. Cell. Biol., April 1, 1998; 18(4): 1996 - 2003. [Abstract] [Full Text]