Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription. Nucleic Acids Res 1997 Aug 01;25(15):3110-7
Date
08/01/1997Pubmed ID
9224612Pubmed Central ID
PMC146854DOI
10.1093/nar/25.15.3110Scopus ID
2-s2.0-0030837697 (requires institutional sign-in at Scopus site) 233 CitationsAbstract
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.
Author List
Kennett SB, Udvadia AJ, Horowitz JMAuthor
Ava Udvadia BS,PhD Associate Professor in the Biological Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Cell LineDNA-Binding Proteins
Gene Expression Regulation
Humans
Promoter Regions, Genetic
Protein Biosynthesis
Repressor Proteins
Retinoblastoma
Sp3 Transcription Factor
Transcription Factors
Transcription, Genetic
Tumor Cells, Cultured
