This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhu, J. W.
Right arrow Articles by DeGregori, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, J. W.
Right arrow Articles by DeGregori, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2001, p. 8547-8564, Vol. 21, No. 24
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.24.8547-8564.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

E2F1 and E2F2 Determine Thresholds for Antigen-Induced T-Cell Proliferation and Suppress Tumorigenesis

Jing W. Zhu,1 Seth J. Field,2,dagger Lia Gore,3 Margaret Thompson,2 Haidi Yang,2,4 Yuko Fujiwara,2,4 Robert D. Cardiff,5 Michael Greenberg,2 Stuart H. Orkin,2,4 and James DeGregori1,3,6,*

Department of Biochemistry and Molecular Genetics,1 Integrated Department of Immunology,6 and Department of Pediatrics,3 University of Colorado Health Sciences Center, Denver, Colorado 80262; Howard Hughes Medical Institute4 and Division of Neuroscience, Children's Hospital,2 and Department of Neurobiology, Harvard Medical School and Dana Farber Cancer Institute, Boston, Massachusetts 02115; and Center for Comparative Medicine and Department of Pathology, School of Medicine, University of California at Davis, Davis, California 956165

Received 9 August 2001/Returned for modification 24 September 2001/Accepted 2 October 2001

E2F activity is critical for the control of the G1 to S phase transition. We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell proliferation and differentiation, as well as increased tumorigenesis and decreased lymphocyte tolerance. The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic progenitor cells in the bone marrow of mice lacking E2F1 and E2F2 exhibit increased cell cycling. Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry into S phase following antigenic stimulation. Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to subthreshold antigenic stimulation. Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the development of tumors, and some mice exhibit signs of autoimmunity.

* Corresponding author. Mailing address: University of Colorado Health Sciences Ctr. BRB802, 4200 E. Ninth Ave., Denver, CO 80262. Phone: (303)-315-5792. Fax: (303)-315-3244. E-mail: james.degregori{at}uchsc.edu.

dagger Present address: Harvard Institutes of Medicine, Beth Israel Deaconess Hospital, and Division of Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115.

Molecular and Cellular Biology, December 2001, p. 8547-8564, Vol. 21, No. 24
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.24.8547-8564.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Panchanathan, R., Xin, H., Choubey, D. (2008). Disruption of Mutually Negative Regulatory Feedback Loop between Interferon-Inducible p202 Protein and the E2F Family of Transcription Factors in Lupus-Prone Mice. J. Immunol. 180: 5927-5934 [Abstract] [Full Text]  
  • Redmond, W. L., Wei, C.-H., Kreuwel, H. T. C., Sherman, L. A. (2008). The Apoptotic Pathway Contributing to the Deletion of Naive CD8 T Cells during the Induction of Peripheral Tolerance to a Cross-Presented Self-Antigen. J. Immunol. 180: 5275-5282 [Abstract] [Full Text]  
  • Dirlam, A., Spike, B. T., Macleod, K. F. (2007). Deregulated E2f-2 Underlies Cell Cycle and Maturation Defects in Retinoblastoma Null Erythroblasts. Mol. Cell. Biol. 27: 8713-8728 [Abstract] [Full Text]  
  • Saenz-Robles, M. T., Markovics, J. A., Chong, J.-L., Opavsky, R., Whitehead, R. H., Leone, G., Pipas, J. M. (2007). Intestinal Hyperplasia Induced by Simian Virus 40 Large Tumor Antigen Requires E2F2. J. Virol. 81: 13191-13199 [Abstract] [Full Text]  
  • Xu, X., Bieda, M., Jin, V. X., Rabinovich, A., Oberley, M. J., Green, R., Farnham, P. J. (2007). A comprehensive ChIP chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. Genome Res 17: 1550-1561 [Abstract] [Full Text]  
  • Opavsky, R., Tsai, S.-Y., Guimond, M., Arora, A., Opavska, J., Becknell, B., Kaufmann, M., Walton, N. A., Stephens, J. A., Fernandez, S. A., Muthusamy, N., Felsher, D. W., Porcu, P., Caligiuri, M. A., Leone, G. (2007). Specific tumor suppressor function for E2F2 in Myc-induced T cell lymphomagenesis. Proc. Natl. Acad. Sci. USA 104: 15400-15405 [Abstract] [Full Text]  
  • Olivier, S., Close, P., Castermans, E., de Leval, L., Tabruyn, S., Chariot, A., Malaise, M., Merville, M.-P., Bours, V., Franchimont, N. (2006). Raloxifene-Induced Myeloma Cell Apoptosis: A Study of Nuclear Factor-{kappa}B Inhibition and Gene Expression Signature. Mol. Pharmacol. 69: 1615-1623 [Abstract] [Full Text]  
  • DeRyckere, D., DeGregori, J. (2005). E2F1 and E2F2 Are Differentially Required for Homeostasis-Driven and Antigen-Induced T Cell Proliferation In Vivo. J. Immunol. 175: 647-655 [Abstract] [Full Text]  
  • Tominaga, K., Magee, D. M., Matzuk, M. M., Pereira-Smith, O. M. (2004). PAM14, a Novel MRG- and Rb-Associated Protein, Is Not Required for Development and T-Cell Function in Mice. Mol. Cell. Biol. 24: 8366-8373 [Abstract] [Full Text]  
  • Cao, Q., Xia, Y., Azadniv, M., Crispe, I. N. (2004). The E2F-1 Transcription Factor Promotes Caspase-8 and Bid Expression, and Enhances Fas Signaling in T Cells. J. Immunol. 173: 1111-1117 [Abstract] [Full Text]  
  • Scheijen, B., Bronk, M., van der Meer, T., De Jong, D., Bernards, R. (2004). High Incidence of Thymic Epithelial Tumors in E2F2 Transgenic Mice. J. Biol. Chem. 279: 10476-10483 [Abstract] [Full Text]  
  • D'Alo', F., Johansen, L. M., Nelson, E. A., Radomska, H. S., Evans, E. K., Zhang, P., Nerlov, C., Tenen, D. G. (2003). The amino terminal and E2F interaction domains are critical for C/EBP{alpha}-mediated induction of granulopoietic development of hematopoietic cells. Blood 102: 3163-3171 [Abstract] [Full Text]  
  • Li, F. X., Zhu, J. W., Tessem, J. S., Beilke, J., Varella-Garcia, M., Jensen, J., Hogan, C. J., DeGregori, J. (2003). The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss. Proc. Natl. Acad. Sci. USA 100: 12935-12940 [Abstract] [Full Text]  
  • Ziebold, U., Lee, E. Y., Bronson, R. T., Lees, J. A. (2003). E2F3 Loss Has Opposing Effects on Different pRB-Deficient Tumors, Resulting in Suppression of Pituitary Tumors but Metastasis of Medullary Thyroid Carcinomas. Mol. Cell. Biol. 23: 6542-6552 [Abstract] [Full Text]  
  • Kimura, H., Nakamura, T., Ogawa, T., Tanaka, S., Shiota, K. (2003). Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. Nucleic Acids Res 31: 3101-3113 [Abstract] [Full Text]  
  • Li, F. X., Zhu, J. W., Hogan, C. J., DeGregori, J. (2003). Defective Gene Expression, S Phase Progression, and Maturation during Hematopoiesis in E2F1/E2F2 Mutant Mice. Mol. Cell. Biol. 23: 3607-3622 [Abstract] [Full Text]  
  • Scheijen, B., Bronk, M., van der Meer, T., Bernards, R. (2003). Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation. Mol. Cell. Biol. 23: 3656-3668 [Abstract] [Full Text]  
  • Kohn, M. J., Bronson, R. T., Harlow, E., Dyson, N. J., Yamasaki, L. (2003). Dp1 is required for extra-embryonic development. Development 130: 1295-1305 [Abstract] [Full Text]  
  • Petrenko, O., Fingerle-Rowson, G., Peng, T., Mitchell, R. A., Metz, C. N. (2003). Macrophage Migration Inhibitory Factor Deficiency Is Associated with Altered Cell Growth and Reduced Susceptibility to Ras-mediated Transformation. J. Biol. Chem. 278: 11078-11085 [Abstract] [Full Text]  
  • Cayirlioglu, P., Ward, W. O., Silver Key, S. C., Duronio, R. J. (2003). Transcriptional Repressor Functions of Drosophila E2F1 and E2F2 Cooperate To Inhibit Genomic DNA Synthesis in Ovarian Follicle Cells. Mol. Cell. Biol. 23: 2123-2134 [Abstract] [Full Text]  
  • Cloud, J. E., Rogers, C., Reza, T. L., Ziebold, U., Stone, J. R., Picard, M. H., Caron, A. M., Bronson, R. T., Lees, J. A. (2002). Mutant Mouse Models Reveal the Relative Roles of E2F1 and E2F3 In Vivo. Mol. Cell. Biol. 22: 2663-2672 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»