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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T. R. Hughes, T. S. Tengku-Muhammad, S. A. Irvine, and D. P. Ramji A Novel Role of Sp1 and Sp3 in the Interferon-gamma -mediated Suppression of Macrophage Lipoprotein Lipase Gene Transcription J. Biol. Chem., March 22, 2002; 277(13): 11097 - 11106. [Abstract] [Full Text] [PDF]
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S. B. Kennett, K. S. Moorefield, and J. M. Horowitz Sp3 Represses Gene Expression via the Titration of Promoter-specific Transcription Factors J. Biol. Chem., March 15, 2002; 277(12): 9780 - 9789. [Abstract] [Full Text] [PDF]
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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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I. Lacroix, C. Lipcey, J. Imbert, and B. Kahn-Perles Sp1 Transcriptional Activity Is Up-regulated by Phosphatase 2A in Dividing T Lymphocytes J. Biol. Chem., March 8, 2002; 277(11): 9598 - 9605. [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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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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