![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, No. 6, pp. 690-703, March 15, 2000
Center for Cancer Research and Department of Biology, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139 USA
E2F is a family of transcription factors that regulate both cellular
proliferation and differentiation. To establish the role of E2F3 in
vivo, we generated an E2f3 mutant mouse strain. E2F3-deficient mice arise at one-quarter of the expected frequency, demonstrating that
E2F3 is important for normal development. To determine the molecular
consequences of E2F3 deficiency, we analyzed the properties of
embryonic fibroblasts derived from E2f3 mutant mice. Mutation of E2f3 dramatically impairs the mitogen-induced,
transcriptional activation of numerous E2F-responsive genes. We have
been able to identify a number of genes, including B-myb,
cyclin A, cdc2, cdc6, and DHFR, whose
expression is dependent on the presence of E2F3 but not E2F1. We
further show that a critical threshold level of one or more of the
E2F3-regulated genes determines the timing of the
G1/S transition, the rate of DNA synthesis, and thereby the rate of cellular proliferation. Finally, we show that E2F3
is not required for cellular immortalization but is rate limiting for
the proliferation of the resulting tumor cell lines. We conclude that
E2F3 is critical for the transcriptional activation of genes that
control the rate of proliferation of both primary and tumor cells.
[Key Words: E2f3; cellular proliferation; transcription]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. R. Andrechek, S. Mori, R. E. Rempel, J. T. Chang, and J. R. Nevins Patterns of cell signaling pathway activation that characterize mammary development Development, July 15, 2008; 135(14): 2403 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Truscott, R. Harada, C. Vadnais, F. Robert, and A. Nepveu p110 CUX1 Cooperates with E2F Transcription Factors in the Transcriptional Activation of Cell Cycle-Regulated Genes Mol. Cell. Biol., May 15, 2008; 28(10): 3127 - 3138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kikuchi, R. Shimizu, T. Wada, H. Ando, M. Nakamura, K. Ozawa, and Y. Furukawa E2F-6 Suppresses Growth-Associated Apoptosis of Human Hematopoietic Progenitor Cells by Counteracting Proapoptotic Activity of E2F-1 Stem Cells, October 1, 2007; 25(10): 2439 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. McClellan, V. A. Ruzhynsky, D. N. Douda, J. L. Vanderluit, K. L. Ferguson, D. Chen, R. Bremner, D. S. Park, G. Leone, and R. S. Slack Unique Requirement for Rb/E2F3 in Neuronal Migration: Evidence for Cell Cycle-Independent Functions Mol. Cell. Biol., July 1, 2007; 27(13): 4825 - 4843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Parisi, T. L. Yuan, A. M. Faust, A. M. Caron, R. Bronson, and J. A. Lees Selective Requirements for E2f3 in the Development and Tumorigenicity of Rb-Deficient Chimeric Tissues Mol. Cell. Biol., March 15, 2007; 27(6): 2283 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lu, T. Bonome, Y. Li, A. A. Kamat, L. Y. Han, R. Schmandt, R. L. Coleman, D. M. Gershenson, R. B. Jaffe, M. J. Birrer, et al. Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma Cancer Res., February 15, 2007; 67(4): 1757 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Woods, J. M. Thomson, and S. M. Hammond Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors J. Biol. Chem., January 26, 2007; 282(4): 2130 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Qiao, L. Di Stefano, C. Tian, Y.-Y. Li, Y.-H. Yin, X.-P. Qian, X.-W. Pang, Y. Li, M. A. McNutt, K. Helin, et al. Human TFDP3, a Novel DP Protein, Inhibits DNA Binding and Transactivation by E2F J. Biol. Chem., January 5, 2007; 282(1): 454 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sharma, C. Timmers, P. Trikha, H. I. Saavedra, A. Obery, and G. Leone Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 Is Essential for G1/S Progression and Cellular Transformation J. Biol. Chem., November 24, 2006; 281(47): 36124 - 36131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Rodriguez, M. A. Glozak, Y. Ma, and W. D. Cress Bok, Bcl-2-related Ovarian Killer, Is Cell Cycle-regulated and Sensitizes to Stress-induced Apoptosis J. Biol. Chem., August 11, 2006; 281(32): 22729 - 22735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. B. Nijman, E. M. Hijmans, S. E. Messaoudi, M. M. W. van Dongen, C. Sardet, and R. Bernards A Functional Genetic Screen Identifies TFE3 as a Gene That Confers Resistance to the Anti-proliferative Effects of the Retinoblastoma Protein and Transforming Growth Factor-beta J. Biol. Chem., August 4, 2006; 281(31): 21582 - 21587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Kinross, A. J. Clark, R. M. Iazzolino, and P. O. Humbert E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation Blood, August 1, 2006; 108(3): 886 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Louie, A. S. Revenko, J. X. Zou, J. Yao, and H.-W. Chen Direct Control of Cell Cycle Gene Expression by Proto-Oncogene Product ACTR, and Its Autoregulation Underlies Its Transforming Activity Mol. Cell. Biol., May 15, 2006; 26(10): 3810 - 3823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sozzani, C. Maggio, S. Varotto, S. Canova, C. Bergounioux, D. Albani, and R. Cella Interplay between Arabidopsis Activating Factors E2Fb and E2Fa in Cell Cycle Progression and Development Plant Physiology, April 1, 2006; 140(4): 1355 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Hallstrom and J. R. Nevins Jab1 is a specificity factor for E2F1-induced apoptosis Genes & Dev., March 1, 2006; 20(5): 613 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bonome, J.-Y. Lee, D.-C. Park, M. Radonovich, C. Pise-Masison, J. Brady, G. J. Gardner, K. Hao, W. H. Wong, J. C. Barrett, et al. Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary Cancer Res., November 15, 2005; 65(22): 10602 - 10612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Walker, Z.-Q. Zhou, S. Ota, A. Wynshaw-Boris, and P. J. Hurlin Mnt-Max to Myc-Max complex switching regulates cell cycle entry J. Cell Biol., May 9, 2005; 169(3): 405 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Denchi, C. Attwooll, D. Pasini, and K. Helin Deregulated E2F Activity Induces Hyperplasia and Senescence-Like Features in the Mouse Pituitary Gland Mol. Cell. Biol., April 1, 2005; 25(7): 2660 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Vilaboa, R. Bermejo, P. Martinez, R. Bornstein, and C. Cales A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization Nucleic Acids Res., December 8, 2004; 32(21): 6454 - 6467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Y. Chang, D. M. Bryce, S. J. A. D'Souza, and L. Dagnino The DP-1 Transcription Factor Is Required for Keratinocyte Growth and Epidermal Stratification J. Biol. Chem., December 3, 2004; 279(49): 51343 - 51353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Lipsick synMuv verite--Myb comes into focus Genes & Dev., December 1, 2004; 18(23): 2837 - 2844. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Karakaidos, S. Taraviras, L. V. Vassiliou, P. Zacharatos, N. G. Kastrinakis, D. Kougiou, M. Kouloukoussa, H. Nishitani, A. G. Papavassiliou, Z. Lygerou, et al. Overexpression of the Replication Licensing Regulators hCdt1 and hCdc6 Characterizes a Subset of Non-Small-Cell Lung Carcinomas: Synergistic Effect with Mutant p53 on Tumor Growth and Chromosomal Instability--Evidence of E2F-1 Transcriptional Control over hCdt1 Am. J. Pathol., October 1, 2004; 165(4): 1351 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Clark, K. M. Doyle, and P. O. Humbert Cell-intrinsic requirement for pRb in erythropoiesis Blood, September 1, 2004; 104(5): 1324 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kohn, S. W. Leung, V. Criniti, M. Agromayor, and L. Yamasaki Dp1 Is Largely Dispensable for Embryonic Development Mol. Cell. Biol., August 15, 2004; 24(16): 7197 - 7205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aslanian, P. J. Iaquinta, R. Verona, and J. A. Lees Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics Genes & Dev., June 15, 2004; 18(12): 1413 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Joyce, D. L. Harris, J. C. Mc Alister, R. R. Ali, and D. F. P. Larkin Effect of Overexpressing the Transcription Factor E2F2 on Cell Cycle Progression in Rabbit Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1340 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Scheijen, M. Bronk, T. van der Meer, D. De Jong, and R. Bernards High Incidence of Thymic Epithelial Tumors in E2F2 Transgenic Mice J. Biol. Chem., March 12, 2004; 279(11): 10476 - 10483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. H. Wang, T. Schmidt, J. Chen, P. A. Sharp, and D. Tantin Embryonic Lethality, Decreased Erythropoiesis, and Defective Octamer-Dependent Promoter Activation in Oct-1-Deficient Mice Mol. Cell. Biol., February 1, 2004; 24(3): 1022 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Hallstrom and J. R. Nevins Specificity in the activation and control of transcription factor E2F-dependent apoptosis PNAS, September 16, 2003; 100(19): 10848 - 10853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Ziebold, E. Y. Lee, R. T. Bronson, and J. A. Lees 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., September 15, 2003; 23(18): 6542 - 6552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kimura, T. Nakamura, T. Ogawa, S. Tanaka, and K. Shiota Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways Nucleic Acids Res., June 15, 2003; 31(12): 3101 - 3113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Giangrande, T. C. Hallstrom, C. Tunyaplin, K. Calame, and J. R. Nevins Identification of E-Box Factor TFE3 as a Functional Partner for the E2F3 Transcription Factor Mol. Cell. Biol., June 1, 2003; 23(11): 3707 - 3720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Veltman, J. Fridlyand, S. Pejavar, A. B. Olshen, J. E. Korkola, S. DeVries, P. Carroll, W.-L. Kuo, D. Pinkel, D. Albertson, et al. Array-based Comparative Genomic Hybridization for Genome-Wide Screening of DNA Copy Number in Bladder Tumors Cancer Res., June 1, 2003; 63(11): 2872 - 2880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. X. Li, J. W. Zhu, C. J. Hogan, and J. DeGregori Defective Gene Expression, S Phase Progression, and Maturation during Hematopoiesis in E2F1/E2F2 Mutant Mice Mol. Cell. Biol., May 15, 2003; 23(10): 3607 - 3622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Scheijen, M. Bronk, T. van der Meer, and R. Bernards Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation Mol. Cell. Biol., May 15, 2003; 23(10): 3656 - 3668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gao, A. P. Bracken, K. Burkard, D. Pasini, M. Classon, C. Attwooll, M. Sagara, T. Imai, K. Helin, and J. Zhao NPAT Expression Is Regulated by E2F and Is Essential for Cell Cycle Progression Mol. Cell. Biol., April 15, 2003; 23(8): 2821 - 2833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. MUNDLE and G. SABERWAL Evolving intricacies and implications of E2F1 regulation FASEB J, April 1, 2003; 17(6): 569 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Kohn, R. T. Bronson, E. Harlow, N. J. Dyson, and L. Yamasaki Dp1 is required for extra-embryonic development Development, April 1, 2003; 130(7): 1295 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Petrenko, G. Fingerle-Rowson, T. Peng, R. A. Mitchell, and C. N. Metz Macrophage Migration Inhibitory Factor Deficiency Is Associated with Altered Cell Growth and Reduced Susceptibility to Ras-mediated Transformation J. Biol. Chem., March 21, 2003; 278(13): 11078 - 11085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cayirlioglu, W. O. Ward, S. C. Silver Key, and R. J. Duronio Transcriptional Repressor Functions of Drosophila E2F1 and E2F2 Cooperate To Inhibit Genomic DNA Synthesis in Ovarian Follicle Cells Mol. Cell. Biol., March 15, 2003; 23(6): 2123 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Landsberg, J. E. Sero, P. S. Danielian, T. L. Yuan, E. Y. Lee, and J. A. Lees The role of E2F4 in adipogenesis is independent of its cell cycle regulatory activity PNAS, March 4, 2003; 100(5): 2456 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Catchpole, F. Tavner, L. Le Cam, C. Sardet, and R. J. Watson A B-myb Promoter Corepressor Site Facilitates in Vivo Occupation of the Adjacent E2F Site by p107{middle dot}E2F and p130{middle dot}E2F Complexes J. Biol. Chem., October 4, 2002; 277(41): 39015 - 39024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fujita, Y. Furukawa, N. Itabashi, K. Okada, T. Saito, and S. Ishibashi Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H204 - H212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. He and W. D. Cress E2F-3B Is a Physiological Target of Cyclin A J. Biol. Chem., June 21, 2002; 277(26): 23493 - 23499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. I. Saavedra, L. Wu, A. de Bruin, C. Timmers, T. J. Rosol, M. Weinstein, M. L. Robinson, and G. Leone Specificity of E2F1, E2F2, and E2F3 in Mediating Phenotypes Induced by Loss of Rb Cell Growth Differ., May 1, 2002; 13(5): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Cloud, C. Rogers, T. L. Reza, U. Ziebold, J. R. Stone, M. H. Picard, A. M. Caron, R. T. Bronson, and J. A. Lees Mutant Mouse Models Reveal the Relative Roles of E2F1 and E2F3 In Vivo Mol. Cell. Biol., April 15, 2002; 22(8): 2663 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Rayman, Y. Takahashi, V. B. Indjeian, J.-H. Dannenberg, S. Catchpole, R. J. Watson, H. te Riele, and B. D. Dynlacht E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex Genes & Dev., April 15, 2002; 16(8): 933 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ren, H. Cam, Y. Takahashi, T. Volkert, J. Terragni, R. A. Young, and B. D. Dynlacht E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints Genes & Dev., January 15, 2002; 16(2): 245 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-K. Hsieh, D. Yap, D. J. O'Connor, V. Fogal, L. Fallis, F. Chan, S. Zhong, and X. Lu Novel Function of the Cyclin A Binding Site of E2F in Regulating p53-Induced Apoptosis in Response to DNA Damage Mol. Cell. Biol., January 1, 2002; 22(1): 78 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Zhu, S. J. Field, L. Gore, M. Thompson, H. Yang, Y. Fujiwara, R. D. Cardiff, M. Greenberg, S. H. Orkin, and J. DeGregori E2F1 and E2F2 Determine Thresholds for Antigen-Induced T-Cell Proliferation and Suppress Tumorigenesis Mol. Cell. Biol., December 15, 2001; 21(24): 8547 - 8564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cayirlioglu, P. C. Bonnette, M. R. Dickson, and R. J. Duronio Drosophila E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells Development, December 15, 2001; 128(24): 5085 - 5098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Frolov, D. S. Huen, O. Stevaux, D. Dimova, K. Balczarek-Strang, M. Elsdon, and N. J. Dyson Functional antagonism between E2F family members Genes & Dev., August 15, 2001; 15(16): 2146 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ishida, E. Huang, H. Zuzan, R. Spang, G. Leone, M. West, and J. R. Nevins Role for E2F in Control of Both DNA Replication and Mitotic Functions as Revealed from DNA Microarray Analysis Mol. Cell. Biol., July 15, 2001; 21(14): 4684 - 4699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Nevins The Rb/E2F pathway and cancer Hum. Mol. Genet., April 1, 2001; 10(7): 699 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Martelli, T. Hamilton, D. P. Silver, N. E. Sharpless, N. Bardeesy, M. Rokas, R. A. DePinho, D. M. Livingston, and S. R. Grossman p19ARF targets certain E2F species for degradation PNAS, March 22, 2001; (2001) 81061398. [Abstract] [Full Text]
|
|
|
|
|
|
S. Gaubatz, J. A. Lees, G. J. Lindeman, and D. M. Livingston E2F4 Is Exported from the Nucleus in a CRM1-Dependent Manner Mol. Cell. Biol., February 15, 2001; 21(4): 1384 - 1392. [Abstract] [Full Text]
|
|
|
|
|
|
U. Ziebold, T. Reza, A. Caron, and J. A. Lees E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos Genes & Dev., February 15, 2001; 15(4): 386 - 391. [Abstract] [Full Text]
|
|
|
|
|
|
H. Müller, A. P. Bracken, R. Vernell, M. C. Moroni, F. Christians, E. Grassilli, E. Prosperini, E. Vigo, J. D. Oliner, and K. Helin E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis Genes & Dev., February 1, 2001; 15(3): 267 - 285. [Abstract] [Full Text]
|
|
