This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martínez-Gac, L. Articles by Carrera, A. C. Search for Related Content PubMed PubMed Citation Articles by Martínez-Gac, L. Articles by Carrera, A. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2004, p. 2181-2189, Vol. 24, No. 5
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.5.2181-2189.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Control of Cyclin G2 mRNA Expression by Forkhead Transcription Factors: Novel Mechanism for Cell Cycle Control by Phosphoinositide 3-Kinase and Forkhead

Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049,¹ Instituto de Investigaciones Biomédicas Alberto Sols, Madrid E-28029, Spain²

Received 21 July 2003/ Returned for modification 29 August 2003/ Accepted 4 December 2003

Cyclin G2 is an unconventional cyclin highly expressed in postmitotic cells. Unlike classical cyclins that promote cell cycle progression, cyclin G2 blocks cell cycle entry. Here we studied the mechanisms that regulate cyclin G2 mRNA expression during the cell cycle. Analysis of synchronized NIH 3T3 cell cultures showed elevated cyclin G2 mRNA expression levels at G₀, with a considerable reduction as cells enter cell cycle. Downregulation of cyclin G2 mRNA levels requires activation of phosphoinositide 3-kinase, suggesting that this enzyme controls cyclin G2 mRNA expression. Because the phosphoinositide 3-kinase pathway inhibits the FoxO family of forkhead transcription factors, we examined the involvement of these factors in the regulation of cyclin G2 expression. We show that active forms of the forkhead transcription factor FoxO3a (FKHRL1) increase cyclin G2 mRNA levels. Cyclin G2 has forkhead consensus motifs in its promoter, which are transactivated by constitutive active FoxO3a forms. Finally, interference with forkhead-mediated transcription by overexpression of an inactive form decreases cyclin G2 mRNA expression levels. These results show that FoxO genes regulate cyclin G2 expression, illustrating a new role for phosphoinositide 3-kinase and FoxO transcription factors in the control of cell cycle entry.

This article has been cited by other articles:

• Yalcin, S., Zhang, X., Luciano, J. P., Mungamuri, S. K., Marinkovic, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R., Ghaffari, S. (2008). Foxo3 Is Essential for the Regulation of Ataxia Telangiectasia Mutated and Oxidative Stress-mediated Homeostasis of Hematopoietic Stem Cells. J. Biol. Chem. 283: 25692-25705 [Abstract] [Full Text]  
• Fabre, S., Carrette, F., Chen, J., Lang, V., Semichon, M., Denoyelle, C., Lazar, V., Cagnard, N., Dubart-Kupperschmitt, A., Mangeney, M., Fruman, D. A., Bismuth, G. (2008). FOXO1 Regulates L-Selectin and a Network of Human T Cell Homing Molecules Downstream of Phosphatidylinositol 3-Kinase. J. Immunol. 181: 2980-2989 [Abstract] [Full Text]  
• Marques, M., Kumar, A., Cortes, I., Gonzalez-Garcia, A., Hernandez, C., Moreno-Ortiz, M. C., Carrera, A. C. (2008). Phosphoinositide 3-Kinases p110{alpha} and p110{beta} Regulate Cell Cycle Entry, Exhibiting Distinct Activation Kinetics in G1 Phase. Mol. Cell. Biol. 28: 2803-2814 [Abstract] [Full Text]  
• Nakae, J., Cao, Y., Oki, M., Orba, Y., Sawa, H., Kiyonari, H., Iskandar, K., Suga, K., Lombes, M., Hayashi, Y. (2008). Forkhead Transcription Factor FoxO1 in Adipose Tissue Regulates Energy Storage and Expenditure. Diabetes 57: 563-576 [Abstract] [Full Text]  
• Cui, M., Huang, Y., Zhao, Y., Zheng, J. (2008). Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages. J. Immunol. 180: 898-906 [Abstract] [Full Text]  
• Le, X.-F., Arachchige-Don, A. S., Mao, W., Horne, M. C., Bast, R. C. Jr. (2007). Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells. Molecular Cancer Therapeutics 6: 2843-2857 [Abstract] [Full Text]  
• Fang, J., Menon, M., Kapelle, W., Bogacheva, O., Bogachev, O., Houde, E., Browne, S., Sathyanarayana, P., Wojchowski, D. M. (2007). EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts. Blood 110: 2361-2370 [Abstract] [Full Text]  
• Delpuech, O., Griffiths, B., East, P., Essafi, A., Lam, E. W.-F., Burgering, B., Downward, J., Schulze, A. (2007). Induction of Mxi1-SR{alpha} by FOXO3a Contributes to Repression of Myc-Dependent Gene Expression. Mol. Cell. Biol. 27: 4917-4930 [Abstract] [Full Text]  
• Bakker, W. J., van Dijk, T. B., Parren-van Amelsvoort, M., Kolbus, A., Yamamoto, K., Steinlein, P., Verhaak, R. G. W., Mak, T. W., Beug, H., Lowenberg, B., von Lindern, M. (2007). Differential Regulation of Foxo3a Target Genes in Erythropoiesis. Mol. Cell. Biol. 27: 3839-3854 [Abstract] [Full Text]  
• Glauser, D. A, Schlegel, W. (2007). The emerging role of FOXO transcription factors in pancreatic {beta} cells. J Endocrinol 193: 195-207 [Abstract] [Full Text]  
• Hinman, R. M., Bushanam, J. N., Nichols, W. A., Satterthwaite, A. B. (2007). B Cell Receptor Signaling Down-Regulates Forkhead Box Transcription Factor Class O 1 mRNA Expression via Phosphatidylinositol 3-Kinase and Bruton's Tyrosine Kinase. J. Immunol. 178: 740-747 [Abstract] [Full Text]  
• Kumar, A., Marques, M., Carrera, A. C. (2006). Phosphoinositide 3-Kinase Activation in Late G1 Is Required for c-Myc Stabilization and S Phase Entry. Mol. Cell. Biol. 26: 9116-9125 [Abstract] [Full Text]  
• Kobayashi, S., Shimamura, T., Monti, S., Steidl, U., Hetherington, C. J., Lowell, A. M., Golub, T., Meyerson, M., Tenen, D. G., Shapiro, G. I., Halmos, B. (2006). Transcriptional Profiling Identifies Cyclin D1 as a Critical Downstream Effector of Mutant Epidermal Growth Factor Receptor Signaling. Cancer Res. 66: 11389-11398 [Abstract] [Full Text]  
• Stossi, F., Likhite, V. S., Katzenellenbogen, J. A., Katzenellenbogen, B. S. (2006). Estrogen-occupied Estrogen Receptor Represses Cyclin G2 Gene Expression and Recruits a Repressor Complex at the Cyclin G2 Promoter. J. Biol. Chem. 281: 16272-16278 [Abstract] [Full Text]  
• Chen, J., Yusuf, I., Andersen, H.-M., Fruman, D. A. (2006). FOXO Transcription Factors Cooperate with {delta}EF1 to Activate Growth Suppressive Genes in B Lymphocytes.. J. Immunol. 176: 2711-2721 [Abstract] [Full Text]  
• Kumar, R. N., Ha, J. H., Radhakrishnan, R., Dhanasekaran, D. N. (2006). Transactivation of Platelet-Derived Growth Factor Receptor {alpha} by the GTPase-Deficient Activated Mutant of G{alpha}12. Mol. Cell. Biol. 26: 50-62 [Abstract] [Full Text]  
• Park, Y., Maizels, E. T., Feiger, Z. J., Alam, H., Peters, C. A., Woodruff, T. K., Unterman, T. G., Lee, E. J., Jameson, J. L., Hunzicker-Dunn, M. (2005). Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad. J. Biol. Chem. 280: 9135-9148 [Abstract] [Full Text]  
• Kim, Y., Shintani, S., Kohno, Y., Zhang, R., Wong, D. T. (2004). Cyclin G2 Dysregulation in Human Oral Cancer. Cancer Res. 64: 8980-8986 [Abstract] [Full Text]  
• Zhu, X., Hart, R., Chang, M. S., Kim, J.-W., Lee, S. Y., Cao, Y. A., Mock, D., Ke, E., Saunders, B., Alexander, A., Grossoehme, J., Lin, K.-M., Yan, Z., Hsueh, R., Lee, J., Scheuermann, R. H., Fruman, D. A., Seaman, W., Subramaniam, S., Sternweis, P., Simon, M. I., Choi, S. (2004). Analysis of the Major Patterns of B Cell Gene Expression Changes in Response to Short-Term Stimulation with 33 Single Ligands. J. Immunol. 173: 7141-7149 [Abstract] [Full Text]  
• You, H., Jang, Y., You-Ten, A. I., Okada, H., Liepa, J., Wakeham, A., Zaugg, K., Mak, T. W. (2004). p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1. Proc. Natl. Acad. Sci. USA 101: 14057-14062 [Abstract] [Full Text]  
• Yusuf, I., Zhu, X., Kharas, M. G., Chen, J., Fruman, D. A. (2004). Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors. Blood 104: 784-787 [Abstract] [Full Text]