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PMID: 11134340 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Id helix-loop-helix proteins antagonize pax transcription factor activity by inhibiting DNA binding.

Molecular and cellular biology ·Vol. 21 ·No. 2 ·2001-01-00 ·Pages 524-33

Roberts EC, Deed RW, Inoue T, Norton JD, Sharrocks AD

Abstract

The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation of cellular proliferation and differentiation. The major mechanism by which Id proteins are thought to inhibit differentiation is through interaction with other HLH proteins and inhibition of their DNA-binding activity. However, Id proteins have also been shown to interact with other proteins involved in regulating cellular proliferation and differentiation, suggesting a more widespread regulatory function. In this study we demonstrate functional interactions between Id proteins and members of the Pax-2/-5/-8 subfamily of paired-domain transcription factors. Members of the Pax transcription factor family have key functions in regulating several developmental processes exemplified by B lymphopoiesis, in which Pax-5 plays an essential role. Id proteins bind to Pax proteins in vitro and in vivo. Binding occurs through the paired DNA-binding domain of the Pax proteins and results in the disruption of DNA-bound complexes containing Pax-2, Pax-5, and Pax-8. In vivo, Id proteins modulate the transcriptional activity mediated by Pax-5 complexes on the B-cell-specific mb-1 promoter. Our results therefore demonstrate a novel facet of Id function in regulating cellular differentiation by functionally antagonizing the action of members of the Pax transcription factor family.

MeSH Terms
3T3 Cells Animals Antigens, CD/genetics Base Sequence CD79 Antigens COS Cells DNA/genetics,metabolism DNA-Binding Proteins/antagonists & inhibitors,metabolism Gene Expression Regulation Helix-Loop-Helix Motifs Inhibitor of Differentiation Protein 1 Inhibitor of Differentiation Protein 2 Inhibitor of Differentiation Proteins Mice Neoplasm Proteins Nuclear Proteins/antagonists & inhibitors,metabolism Oligodeoxyribonucleotides/genetics,metabolism PAX2 Transcription Factor PAX5 Transcription Factor PAX8 Transcription Factor Paired Box Transcription Factors Precipitin Tests Promoter Regions, Genetic/genetics Protein Binding Proto-Oncogene Proteins/metabolism Receptors, Antigen, B-Cell/genetics Repressor Proteins Trans-Activators/antagonists & inhibitors,metabolism Transcription Factors/antagonists & inhibitors,metabolism ets-Domain Protein Elk-1
Chemicals
Antigens, CD CD79 Antigens Cd79a protein, mouse DNA-Binding Proteins Idb1 protein, mouse Idb2 protein, mouse Inhibitor of Differentiation Protein 1 Inhibitor of Differentiation Protein 2 Inhibitor of Differentiation Proteins Neoplasm Proteins Nuclear Proteins Oligodeoxyribonucleotides PAX2 Transcription Factor PAX5 Transcription Factor PAX8 Transcription Factor Paired Box Transcription Factors Pax2 protein, mouse Pax5 protein, mouse Pax8 protein, mouse Proto-Oncogene Proteins Receptors, Antigen, B-Cell Repressor Proteins Trans-Activators Transcription Factors ets-Domain Protein Elk-1 ID3 protein, human DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Roberts E C
Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
Deed R W
Inoue T
Norton J D
Sharrocks A D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.2.524-533.2001
Published
2001-01-00
Pages
524-33
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86614
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.2.524-533.2001 PMC Full Text View journal details
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