Id helix-loop-helix proteins antagonize pax transcription factor activity by inhibiting DNA binding.
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.
Roberts
E C
EC
Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
Deed
R W
RW
Inoue
T
T
Norton
J D
JD
Sharrocks
A D
AD
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D051925:CD79 Antigens; D019556:COS Cells; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D004268:DNA-Binding Proteins; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C497319:Pax2 protein, mouse; C497282:Pax5 protein, mouse; C499496:Pax8 protein, mouse; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C075640:ID3 protein, human; D004247:DNA