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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sala, A. Articles by Calabretta, B. Search for Related Content PubMed PubMed Citation Articles by Sala, A. Articles by Calabretta, B.

Correlation between E2F-1 Requirement in the S Phase and E2F-1 Transactivation of Cell Cycle-related Genes in Human Cells¹

Jefferson Cancer Institute and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia Pennsylvania 19107 [A. S., N. C. N., A. E., T. B., D. C. L., B. C.] Endocrine Oncology Unit, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts 02114 [A. A.] and Fels Institute for Cancer Research and Molecular Biology and Department of Pathology and Biochemistry, Temple University, Philadelphia Pennsylvania 19140 [X. G., A. G.]

The mammalian nuclear protein E2F-1 has recently been cloned based on its ability to bind the retinoblastoma protein. To determine whether E2F-1 plays a role in the control of the cell proliferation, we introduced an inducible construct expressing an E2F-1 antisense RNA into the human glioblastoma T98G cell line and assessed DNA synthesis during the cell cycle. Expression of the antisense transcripts during the G₁-S transition resulted in a marked delay in the completion of DNA synthesis. Band-shift analysis of bacterially produced E2F-1 showed that this protein bound to the promoters of human DNA polymerase-, cyclin D1, and c-myb but not to the cdc2 gene promoter. E2F-1 also transactivated the bound promoters in transient transfection assays. These results suggest a major role for E2F-1 in the control of cell cycle progression via transcriptional regulation of proliferation-associated genes.

¹ This work was supported by NIH and ACS grants (B. C.); by grants from W. W. Smith Charitable Trust, the Milheim Foundation, and the L. Markey Charitable Trust (A.G.); and by NIH grant CA55909 and ACS grant FRA-391 (A. A.). X. G. was supported by a fellowship from the Spanish Ministry of Education and Science under the MEC/Fulbright program and by a fellowship of the Interdepartmental Commission for Research and Technology from "Generalitat de Catalunya." B. C. is a scholar of the Leukemia Society of America.

² Present address: The Johns Hopkins Oncology Center, Baltimore, MD 20892.

³ To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Thomas Jefferson University, 469 Jefferson Alum. Hall, 1020 Locust Street, Philadelphia, PA 19107-6799.

Received 11/17/93. Accepted 2/ 4/94.

This article has been cited by other articles:

				T. Fukushima, T. Nedachi, H. Akizawa, M. Akahori, F. Hakuno, and S.-I. Takahashi Distinct Modes of Activation of Phosphatidylinositol 3-Kinase in Response to Cyclic Adenosine 3', 5'-Monophosphate or Insulin-Like Growth Factor I Play Different Roles in Regulation of Cyclin D1 and p27Kip1 in FRTL-5 Cells Endocrinology, July 1, 2008; 149(7): 3729 - 3742. [Abstract] [Full Text] [PDF]

				J. N. Davis, M. T. McCabe, S. W. Hayward, J. M. Park, and M. L. Day Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells Cancer Res., May 1, 2005; 65(9): 3633 - 3642. [Abstract] [Full Text] [PDF]

				A. Lauder, A. Castellanos, and K. Weston c-myb Transcription Is Activated by Protein Kinase B (PKB) following Interleukin 2 Stimulation of T Cells and Is Required for PKB-Mediated Protection from Apoptosis Mol. Cell. Biol., September 1, 2001; 21(17): 5797 - 5805. [Abstract] [Full Text] [PDF]

				D. Huang, M. Jokela, J. Tuusa, S. Skog, K. Poikonen, and J. E. Syvaoja E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase {{epsilon}} B-subunit gene POLE2 Nucleic Acids Res., July 1, 2001; 29(13): 2810 - 2821. [Abstract] [Full Text] [PDF]

				M. R. Campanero, M. Armstrong, and E. Flemington Distinct Cellular Factors Regulate the c-myb Promoter through Its E2F Element Mol. Cell. Biol., December 1, 1999; 19(12): 8442 - 8450. [Abstract] [Full Text] [PDF]

				M. G. Davenport and J. S. Pagano Expression of EBNA-1 mRNA Is Regulated by Cell Cycle during Epstein-Barr Virus Type I Latency J. Virol., April 1, 1999; 73(4): 3154 - 3161. [Abstract] [Full Text]

				A. Sala, M. Kundu, I. Casella, A. Engelhard, B. Calabretta, L. Grasso, M. G. Paggi, A. Giordano, R. J. Watson, K. Khalili, et al. Activation of human B-MYB by cyclins PNAS, January 21, 1997; 94(2): 532 - 536. [Abstract] [Full Text] [PDF]

				J. Sullivan, B. Feeley, J. Guerra, and L. M. Boxer Identification of the Major Positive Regulators of c-myb Expression in Hematopoietic Cells of Different Lineages J. Biol. Chem., January 17, 1997; 272(3): 1943 - 1949. [Abstract] [Full Text] [PDF]

				H. Chen, J. Campisi, and R. Padmanabhan SV40 Large T Antigen Transactivates the Human cdc2 Promoter by Inducing a CCAAT Box Binding Factor J. Biol. Chem., June 14, 1996; 271(24): 13959 - 13967. [Abstract] [Full Text] [PDF]

				A. Sala, I. Casella, T. Bellon, B. Calabretta, R. J. Watson, and C. Peschle B-myb Promotes S Phase and Is a Downstream Target of the Negative Regulator p107 in Human Cells J. Biol. Chem., April 19, 1996; 271(16): 9363 - 9367. [Abstract] [Full Text] [PDF]

				A. Hwang, A. Maity, W. G. McKenna, and R. J. Muschel Cell Cycle-dependent Regulation of the Cyclin B1 Promoter J. Biol. Chem., November 24, 1995; 270(47): 28419 - 28424. [Abstract] [Full Text] [PDF]

				K. Fujise, D. Zhang, J.-l. Liu, and E. T. H. Yeh Regulation of Apoptosis and Cell Cycle Progression by MCL1. DIFFERENTIAL ROLE OF PROLIFERATING CELL NUCLEAR ANTIGEN J. Biol. Chem., December 8, 2000; 275(50): 39458 - 39465. [Abstract] [Full Text] [PDF]