This Article 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 Chittenden, T Articles by DeCaprio, J A Search for Related Content PubMed PubMed Citation Articles by Chittenden, T Articles by DeCaprio, J A

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 July; 13(7): 3975-3983

Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F.

Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

ABSTRACT

The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene. Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2. We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells. Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes. One of these activities was found to be a novel, less abundant, Rb-E2F complex. The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function. Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2. However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an E1A-binding protein other than Rb or p107. In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments. These species showed different cell cycle kinetics. UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb. Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle.

This article has been cited by other articles:

• Russo, G., Zamparelli, A., Howard, C. M., Minimo, C., Bellan, C., Carillo, G., Califano, L., Leoncini, L., Giordano, A., Claudio, P. P. (2005). Expression of Cell Cycle-Regulated Proteins pRB2/p130, p107, E2F4, p27, and pCNA in Salivary Gland Tumors: Prognostic and Diagnostic Implications. Clin. Cancer Res. 11: 3265-3273 [Abstract] [Full Text]  
• LeCouter, J. E., Kablar, B., Hardy, W. R., Ying, C., Megeney, L. A., May, L. L., Rudnicki, M. A. (1998). Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene. Mol. Cell. Biol. 18: 7455-7465 [Abstract] [Full Text]  
• Thomas, N. S. B., Pizzey, A. R., Tiwari, S., Williams, C. D., Yang, J. (1998). p130, p107, and pRb Are Differentially Regulated in Proliferating Cells and during Cell Cycle Arrest by alpha -Interferon. J. Biol. Chem. 273: 23659-23667 [Abstract] [Full Text]  
• Dyson, N. (1998). The regulation of E2F by pRB-family proteins. Genes Dev. 12: 2245-2262 [Full Text]  
• Dong, F., Cress, W. D. Jr., Agrawal, D., Pledger, W. J. (1998). The Role of Cyclin D3-dependent Kinase in the Phosphorylation of p130 in Mouse BALB/c 3T3 Fibroblasts. J. Biol. Chem. 273: 6190-6195 [Abstract] [Full Text]  
• Harris, K. F., Christensen, J. B., Radany, E. H., Imperiale, M. J. (1998). Novel Mechanisms of E2F Induction by BK Virus Large-T Antigen: Requirement of Both the pRb-Binding and the J Domains. Mol. Cell. Biol. 18: 1746-1756 [Abstract] [Full Text]  
• Mulligan, G. J., Wong, J., Jacks, T. (1998). p130 Is Dispensable in Peripheral T Lymphocytes: Evidence for Functional Compensation by p107 and pRB. Mol. Cell. Biol. 18: 206-220 [Abstract] [Full Text]  
• Williams, C. D., Linch, D. C., Watts, M. J., Thomas, N. S. B. (1997). Characterization of Cell Cycle Status and E2F Complexes in Mobilized CD34+ Cells Before and After Cytokine Stimulation. Blood 90: 194-203 [Abstract] [Full Text]  
• Eid, J. E., Sollner-Webb, B. (1997). ST-2, a Telomere and Subtelomere Duplex and G-strand Binding Protein Activity in Trypanosoma brucei. J. Biol. Chem. 272: 14927-14936 [Abstract] [Full Text]  
• Hurford, R K, Cobrinik, D, Lee, M H, Dyson, N (1997). pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes.. Genes Dev. 11: 1447-1463 [Abstract]  
• Hateboer, G, Kerkhoven, R M, Shvarts, A, Bernards, R, Beijersbergen, R L (1996). Degradation of E2F by the ubiquitin-proteasome pathway: regulation by retinoblastoma family proteins and adenovirus transforming proteins.. Genes Dev. 10: 2960-2970 [Abstract]  
• Freter, R. R., Alberta, J. A., Hwang, G. Y., Wrentmore, A. L., Stiles, C. D. (1996). Platelet-derived Growth Factor Induction of the Immediate-early gene MCP-1 Is Mediated by NF-kappa B and a 90-kDa Phosphoprotein Coactivator. J. Biol. Chem. 271: 17417-17424 [Abstract] [Full Text]  
• Magae, J, Wu, C., Illenye, S, Harlow, E, Heintz, N. (1996). Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members. J. Cell Sci. 109: 1717-1726 [Abstract]  
• Johnson, E. M., Chen, P.-L., Krachmarov, C. P., Barr, S. M., Kanovsky, M., Ma, Z.-W., Lee, W.-H. (1995). Association of Human Puralpha with the Retinoblastoma Protein, Rb, Regulates Binding to the Single-stranded DNA Puralpha Recognition Element. J. Biol. Chem. 270: 24352-24360 [Abstract] [Full Text]  
• Yagi, H., Kato, T., Nagata, T., Habu, T., Nozaki, M., Matsushiro, A., Nishimune, Y., Morita, T. (1995). Regulation of the Mouse Histone H2A.X Gene Promoter by the Transcription Factor E2F and CCAAT Binding Protein. J. Biol. Chem. 270: 18759-18765 [Abstract] [Full Text]  
• Vairo, G, Livingston, D M, Ginsberg, D (1995). Functional interaction between E2F-4 and p130: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members.. Genes Dev. 9: 869-881 [Abstract]  
• Hao, X., Alphey, L, Bandara, L., Lam, E., Glover, D, La Thangue, N. (1995). Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. J. Cell Sci. 108: 2945-2954 [Abstract]  
• Ginsberg, D, Vairo, G, Chittenden, T, Xiao, Z X, Xu, G, Wydner, K L, DeCaprio, J A, Lawrence, J B, Livingston, D M (1994). E2F-4, a new member of the E2F transcription factor family, interacts with p107.. Genes Dev. 8: 2665-2679 [Abstract]  
• Johnson, D G, Ohtani, K, Nevins, J R (1994). Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression.. Genes Dev. 8: 1514-1525 [Abstract]  
• Hsiao, K M, McMahon, S L, Farnham, P J (1994). Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter.. Genes Dev. 8: 1526-1537 [Abstract]  
• Cobrinik, D, Whyte, P, Peeper, D S, Jacks, T, Weinberg, R A (1993). Cell cycle-specific association of E2F with the p130 E1A-binding protein.. Genes Dev. 7: 2392-2404 [Abstract]  
• Smith, E., Redman, R. A., Logg, C. R., Coetzee, G. A., Kasahara, N., Frenkel, B. (2000). Glucocorticoids Inhibit Developmental Stage-specific Osteoblast Cell Cycle. DISSOCIATION OF CYCLIN A-CYCLIN-DEPENDENT KINASE 2 FROM E2F4-p130 COMPLEXES. J. Biol. Chem. 275: 19992-20001 [Abstract] [Full Text]