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PMID: 11438660 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

Molecular and cellular biology ·Vol. 21 ·No. 15 ·2001-08-00 ·Pages 5041-9

Zhang JS, Moncrieffe MC, Kaczynski J, Ellenrieder V, Prendergast FG, Urrutia R

Abstract

Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (alpha-HRM) located within the repression domain (R1) of TIEG2. This alpha-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 alpha-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the alpha-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The alpha-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the alpha-HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the alpha-HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Animals Apoptosis Regulatory Proteins Blotting, Western CHO Cells Cell Cycle Proteins/chemistry,metabolism Cell Division Circular Dichroism Cricetinae Genetic Vectors Glutathione Transferase/metabolism Luciferases/metabolism Molecular Sequence Data Mutation Peptide Biosynthesis Plasmids/metabolism Precipitin Tests Protein Binding Protein Biosynthesis Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism Repressor Proteins/chemistry,metabolism Sequence Homology, Amino Acid Sin3 Histone Deacetylase and Corepressor Complex Sp1 Transcription Factor/chemistry Transcription, Genetic Transforming Growth Factor beta/metabolism Zinc Fingers
Chemicals
Apoptosis Regulatory Proteins Cell Cycle Proteins KLF11 protein, human Recombinant Fusion Proteins Repressor Proteins SIN3A transcription factor Sp1 Transcription Factor Transforming Growth Factor beta Luciferases Glutathione Transferase Sin3 Histone Deacetylase and Corepressor Complex
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhang J S
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55901, USA.
Moncrieffe M C
Kaczynski J
Ellenrieder V
Prendergast F G
Urrutia R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.15.5041-5049.2001
Published
2001-08-00
Pages
5041-9
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC87230
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052913 · United States
NIDDK NIH HHS · R01 DK052913-06 · United States
NIDDK NIH HHS · R56 DK052913 · United States
NIDDK NIH HHS · DK52913 · United States
External Links
PubMed source DOI: 10.1128/MCB.21.15.5041-5049.2001 PMC Full Text View journal details
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