Nucleic Acids Research, Vol 25, Issue 15 3110-3117, Copyright © 1997 by Oxford University Press
SB Kennett, AJ Udvadia and JM Horowitz
The product of the retinoblastoma (Rb) susceptibility gene ( RB-1 )
regulates expression of a variety of growth control genes via discrete
promoter elements termed retinoblastoma control elements (RCEs). We have
previously shown that RCEs are bound and regulated by a common set of
ubiquitously expressed nuclear proteins of 115, 95 and 80 kDa, termed
retinoblastoma control proteins (RCPs). We have also previously determined
that Sp3 and Sp1, two members of the Sp family of transcription factors,
encode the 115 and 95 kDa RCPs respectively and that Rb stimulates
Sp1/Sp3-mediated transcription in vivo. In this report we have extended
these results by determining that the 80 kDa RCP arises from Sp3 mRNA via
translational initiation at two internal sites located within the Sp3 trans
-activation domain. Internally initiated Sp3 proteins readily bind to Sp1
binding sites in vitro yet have little or no capacity to stimulate
transcription of Sp-regulated genes in vivo. Instead, these Sp3-derived
proteins function as potent inhibitors of Sp1/Sp3- mediated transcription.
Since cell cycle- or signal- induced expression of a variety of genes,
including p21 waf1/cip1, p15 INK4B, CYP11A, mdr1 and acetyl-CoA
carboxylase, have been mapped to GC-rich promoter elements that bind Sp
family members, we speculate that alterations of the protein and/or DNA
binding activities of internally initiated Sp3 isoforms may account in part
for the regulation of such differentially expressed genes.
ARTICLES
Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription
Departments of Molecular Cancer Biology and Microbiology, Box 3686, Duke University Medical Center, Durham, NC 27710, USA.
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S.-P. Wang, I. Krits, S. Bai, and B. S. Lee Regulation of Enhanced Vacuolar H+-ATPase Expression in Macrophages J. Biol. Chem., March 8, 2002; 277(11): 8827 - 8834. [Abstract] [Full Text] [PDF]
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K. J. Kolell and D. L. Crawford Evolution of Sp Transcription Factors Mol. Biol. Evol., March 1, 2002; 19(3): 216 - 222. [Abstract] [Full Text] [PDF]
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S. Ross, A. Tienhaara, M.-S. Lee, L.-H. Tsai, and G. Gill GC Box-binding Transcription Factors Control the Neuronal Specific Transcription of the Cyclin-dependent Kinase 5 Regulator p35 J. Biol. Chem., February 1, 2002; 277(6): 4455 - 4464. [Abstract] [Full Text] [PDF]
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T. Ragoczy and G. Miller Autostimulation of the Epstein-Barr Virus BRLF1 Promoter Is Mediated through Consensus Sp1 and Sp3 Binding Sites J. Virol., June 1, 2001; 75(11): 5240 - 5251. [Abstract] [Full Text]
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W. K. Wong, K. Chen, and J. C. Shih Regulation of Human Monoamine Oxidase B Gene by Sp1 and Sp3 Mol. Pharmacol., April 1, 2001; 59(4): 852 - 859. [Abstract] [Full Text]
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K. A. Dellow, P. K. Bhavsar, N. J. Brand, and P. J.R. Barton Identification of novel, cardiac-restricted transcription factors binding to a CACC-box within the human cardiac troponin I promoter Cardiovasc Res, April 1, 2001; 50(1): 24 - 33. [Abstract] [Full Text] [PDF]
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N. Yusa, K. Watanabe, S. Yoshida, N. Shirafuji, S. Shimomura, K. Tani, S. Asano, and N. Sato Transcription factor Sp3 activates the liver/bone/kidney-type alkaline phosphatase promoter in hematopoietic cells J. Leukoc. Biol., November 1, 2000; 68(5): 772 - 777. [Abstract] [Full Text]
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M.-S. Jiang and M. D. Lane Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBPalpha ) gene during adipogenesis PNAS, October 23, 2000; (2000) 220426097. [Abstract] [Full Text]
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O. Loudig, C. Babichuk, J. White, S. Abu-Abed, C. Mueller, and M. Petkovich Cytochrome P450RAI(CYP26) Promoter: A Distinct Composite Retinoic Acid Response Element Underlies the Complex Regulation of Retinoic Acid Metabolism Mol. Endocrinol., September 1, 2000; 14(9): 1483 - 1497. [Abstract] [Full Text]
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C. R. Vines and D. A. Weigent Identification of SP3 as a Negative Regulatory Transcription Factor in the Monocyte Expression of Growth Hormone Endocrinology, March 1, 2000; 141(3): 938 - 946. [Abstract] [Full Text] [PDF]
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J. H. Yu, G. Schwartzbauer, A. Kazlman, and R. K. Menon Role of the Sp Family of Transcription Factors in the Ontogeny of Growth Hormone Receptor Gene Expression J. Biol. Chem., November 26, 1999; 274(48): 34327 - 34336. [Abstract] [Full Text] [PDF]
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C. Ji, Y. Chen, T. L. McCarthy, and M. Centrella Cloning the Promoter for Transforming Growth Factor-beta Type III Receptor. BASAL AND CONDITIONAL EXPRESSION IN FETAL RAT OSTEOBLASTS J. Biol. Chem., October 22, 1999; 274(43): 30487 - 30494. [Abstract] [Full Text] [PDF]
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T. Santalucia, K. R. Boheler, N. J. Brand, U. Sahye, C. Fandos, F. Vinals, J. Ferre, X. Testar, M. Palacin, and A. Zorzano Factors Involved in GLUT-1 Glucose Transporter Gene Transcription in Cardiac Muscle J. Biol. Chem., June 18, 1999; 274(25): 17626 - 17634. [Abstract] [Full Text] [PDF]
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F. Karantzoulis-Fegaras, H. Antoniou, S.-L. M. Lai, G. Kulkarni, C. D'Abreo, G. K. T. Wong, T. L. Miller, Y. Chan, J. Atkins, Y. Wang, et al. Characterization of the Human Endothelial Nitric-oxide Synthase Promoter J. Biol. Chem., January 29, 1999; 274(5): 3076 - 3093. [Abstract] [Full Text] [PDF]
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S. Vallian, K.-V. Chin, and K.-S. Chang The Promyelocytic Leukemia Protein Interacts with Sp1 and Inhibits Its Transactivation of the Epidermal Growth Factor Receptor Promoter Mol. Cell. Biol., December 1, 1998; 18(12): 7147 - 7156. [Abstract] [Full Text]
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Z. J. Tu, R. Kollander, and D. T. Kiang Differential Up-Regulation of Gap Junction Connexin 26 Gene in Mammary and Uterine Tissues: The Role of Sp Transcription Factors Mol. Endocrinol., December 1, 1998; 12(12): 1931 - 1938. [Abstract] [Full Text]
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H. Ungefroren, B. Gellersen, N. B. Krull, and H. Kalthoff Biglycan Gene Expression in the Human Leiomyosarcoma Cell Line SK-UT-1. BASAL AND PROTEIN KINASE A-INDUCED TRANSCRIPTION INVOLVES BINDING OF Sp1-LIKE/Sp3 PROTEINS IN THE PROXIMAL PROMOTER REGION J. Biol. Chem., October 30, 1998; 273(44): 29230 - 29240. [Abstract] [Full Text] [PDF]
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Z.-Z. Hu, L. Zhuang, J. Meng, and M. L. Dufau Transcriptional Regulation of the Generic Promoter III of the Rat Prolactin Receptor Gene by C/EBPbeta and Sp1 J. Biol. Chem., October 2, 1998; 273(40): 26225 - 26235. [Abstract] [Full Text] [PDF]
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J. B. Redell and B. L Tempel Multiple Promoter Elements Interact to Control the Transcription of the Potassium Channel Gene, KCNJ2 J. Biol. Chem., August 28, 1998; 273(35): 22807 - 22818. [Abstract] [Full Text] [PDF]
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K. L. Hoppe and O. L. Francone Binding and functional effects of transcription factors Sp1 and Sp3 on the proximal human lecithin:cholesterol acyltransferase promoter J. Lipid Res., May 1, 1998; 39(5): 969 - 977. [Abstract] [Full Text]
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N. Beohar and S. Kawamoto Transcriptional Regulation of the Human Nonmuscle Myosin II Heavy Chain-A Gene. IDENTIFICATION OF THREE CLUSTERED CIS-ELEMENTS IN INTRON-1 WHICH MODULATE TRANSCRIPTION IN A CELL TYPE- AND DIFFERENTIATION STATE-DEPENDENT MANNER J. Biol. Chem., April 10, 1998; 273(15): 9168 - 9178. [Abstract] [Full Text] [PDF]
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A.-B. Halim, L. LeGros, M. E. Chamberlin, A. Geller, and M. Kotb Regulation of the Human MAT2A Gene Encoding the Catalytic alpha 2 Subunit of Methionine Adenosyltransferase, MAT II. GENE ORGANIZATION, PROMOTER CHARACTERIZATION, AND IDENTIFICATION OF A SITE IN THE PROXIMAL PROMOTER THAT IS ESSENTIAL FOR ITS ACTIVITY J. Biol. Chem., March 23, 2001; 276(13): 9784 - 9791. [Abstract] [Full Text] [PDF]
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S. Ammanamanchi and M. G. Brattain Sp3 Is a Transcriptional Repressor of Transforming Growth Factor-beta Receptors J. Biol. Chem., January 26, 2001; 276(5): 3348 - 3352. [Abstract] [Full Text] [PDF]
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Y. Yang, C. K. Hwang, E. Junn, G. Lee, and M. M. Mouradian ZIC2 and Sp3 Repress Sp1-induced Activation of the Human D1ADopamine Receptor Gene J. Biol. Chem., December 1, 2000; 275(49): 38863 - 38869. [Abstract] [Full Text] [PDF]
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J. R. Whetstine and L. H. Matherly The Basal Promoters for the Human Reduced Folate Carrier Gene Are Regulated by a GC-box and a cAMP-response Element/AP-1-like Element. BASIS FOR TISSUE-SPECIFIC GENE EXPRESSION J. Biol. Chem., February 23, 2001; 276(9): 6350 - 6358. [Abstract] [Full Text] [PDF]
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Y. Inagaki, T. Nemoto, A. Nakao, P. t. Dijke, K. Kobayashi, K. Takehara, and P. Greenwel Interaction between GC Box Binding Factors and Smad Proteins Modulates Cell Lineage-specific alpha 2(I) Collagen Gene Transcription J. Biol. Chem., May 4, 2001; 276(19): 16573 - 16579. [Abstract] [Full Text] [PDF]
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S. J. Baek, J. M. Horowitz, and T. E. Eling Molecular Cloning and Characterization of Human Nonsteroidal Anti-inflammatory Drug-activated Gene Promoter. BASAL TRANSCRIPTION IS MEDIATED BY Sp1 AND Sp3 J. Biol. Chem., August 31, 2001; 276(36): 33384 - 33392. [Abstract] [Full Text] [PDF]
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L. LeGros, A.-B. Halim, M. E. Chamberlin, A. Geller, and M. Kotb Regulation of the Human MAT2B Gene Encoding the Regulatory beta Subunit of Methionine Adenosyltransferase, MAT II J. Biol. Chem., June 29, 2001; 276(27): 24918 - 24924. [Abstract] [Full Text] [PDF]
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D. N. Douglas, V. W. Dolinsky, R. Lehner, and D. E. Vance A Role for Sp1 in the Transcriptional Regulation of Hepatic Triacylglycerol Hydrolase in the Mouse J. Biol. Chem., June 29, 2001; 276(27): 25621 - 25630. [Abstract] [Full Text] [PDF]
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S. Ammanamanchi and M. G. Brattain 5-AzaC Treatment Enhances Expression of Transforming Growth Factor-beta Receptors through Down-regulation of Sp3 J. Biol. Chem., August 24, 2001; 276(35): 32854 - 32859. [Abstract] [Full Text] [PDF]
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T. Saito, Y. Takahashi, H. Hashimoto, and T. Kamataki Novel Transcriptional Regulation of the Human CYP3A7 Gene by Sp1 and Sp3 through Nuclear Factor kappa B-like Element J. Biol. Chem., October 5, 2001; 276(41): 38010 - 38022. [Abstract] [Full Text] [PDF]
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M.-S. Jiang and M. D. Lane Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBPalpha ) gene during adipogenesis PNAS, November 7, 2000; 97(23): 12519 - 12523. [Abstract] [Full Text] [PDF]
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M. D. Layne, S.-F. Yet, K. Maemura, C.-M. Hsieh, X. Liu, B. Ith, M.-E. Lee, and M. A. Perrella Characterization of the Mouse Aortic Carboxypeptidase-Like Protein Promoter Reveals Activity in Differentiated and Dedifferentiated Vascular Smooth Muscle Cells Circ. Res., April 5, 2002; 90(6): 728 - 736. [Abstract] [Full Text] [PDF]
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