Faculty Collaboration Database

Functional interactions between the retinoblastoma (Rb) protein and Sp-family members: superactivation by Rb requires amino acids necessary for growth suppression. Proc Natl Acad Sci U S A 1995 Apr 25;92(9):3953-7

Date

04/25/1995

Pubmed ID

7732011

Pubmed Central ID

PMC42080

DOI

10.1073/pnas.92.9.3953

Scopus ID

2-s2.0-0029000724 (requires institutional sign-in at Scopus site)   200 Citations

Abstract

The transient expression of the retinoblastoma protein (Rb) regulates the transcription of a variety of growth-control genes, including c-fos, c-myc, and the gene for transforming growth factor beta 1 via discrete promoter sequences termed retinoblastoma control elements (RCE). Previous analyses have shown that Sp1 is one of three RCE-binding proteins identified in nuclear extracts and that Rb functionally interacts with Sp1 in vivo, resulting in the "superactivation" of Sp1-mediated transcription. By immunochemical and biochemical criteria, we report that an Sp1-related transcription factor, Sp3, is a second RCE-binding protein. Furthermore, in transient cotransfection assays, we report that Rb "superactivates" Sp3-mediated RCE-dependent transcription in vivo and that levels of superactivation are dependent on the trans-activator (Sp1 or Sp3) studied. Using expression vectors carrying mutated Rb cDNAs, we have identified two portions of Rb required for superactivation: (i) a portion of the Rb "pocket" (amino acids 614-839) previously determined to be required for physical interactions between Rb and transcription factors such as E2F-1 and (ii) a novel amino-terminal region (amino acids 140-202). Since both of these regions of Rb are targets of mutation in human tumors, our data suggest that superactivation of Sp1/Sp3 may play a role in Rb-mediated growth suppression and/or the induction of differentiation.

Author List

Udvadia AJ, Templeton DJ, Horowitz JM

Author

Ava Udvadia BS,PhD Associate Professor in the Biological Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Amino Acids
Animals
Cell Division
Cell Line
DNA-Binding Proteins
Drosophila melanogaster
Female
Gene Expression Regulation
Genes, fos
Genes, myc
Genetic Vectors
Humans
Nuclear Proteins
Oligonucleotide Probes
Plasmids
Promoter Regions, Genetic
Retinoblastoma Protein
Sp1 Transcription Factor
Sp3 Transcription Factor
Transcription Factors
Transcription, Genetic
Transfection
Transforming Growth Factor beta
Tumor Cells, Cultured
Uterine Cervical Neoplasms