This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Roberts, E. C.
Right arrow Articles by Sharrocks, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roberts, E. C.
Right arrow Articles by Sharrocks, A. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2001, p. 524-533, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.524-533.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Id Helix-Loop-Helix Proteins Antagonize Pax Transcription Factor Activity by Inhibiting DNA Binding

E. Claire Roberts,1,dagger Richard W. Deed,2 Toshiaki Inoue,3 John D. Norton,2,3 and Andrew D. Sharrocks1,*

Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH,1 Cancer Research Campaign Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX,2 and Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ,3 United Kingdom

Received 26 October 2000/Accepted 1 November 2000

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.

* Corresponding author. Present address: School of Biological Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. Phone: 0044-161 275 5979. Fax: 0044-161 275 5082. E-mail: a.d.sharrocks{at}man.ac.uk.

dagger Present address: Cardiff School of Biosciences, University of Cardiff, Cardiff CF1 3US, United Kingdom.

Molecular and Cellular Biology, January 2001, p. 524-533, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.524-533.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ji, M., Li, H., Suh, H. C., Klarmann, K. D., Yokota, Y., Keller, J. R. (2008). Id2 intrinsically regulates lymphoid and erythroid development via interaction with different target proteins. Blood 112: 1068-1077 [Abstract] [Full Text]  
  • Zhang, X. K., Moussa, O., LaRue, A., Bradshaw, S., Molano, I., Spyropoulos, D. D., Gilkeson, G. S., Watson, D. K. (2008). The Transcription Factor Fli-1 Modulates Marginal Zone and Follicular B Cell Development in Mice. J. Immunol. 181: 1644-1654 [Abstract] [Full Text]  
  • Man, C., Rosa, J., Yip, Y. L., Cheung, A. L.-M., Kwong, Y. L., Doxsey, S. J., Tsao, S. W. (2008). Id1 Overexpression Induces Tetraploidization and Multiple Abnormal Mitotic Phenotypes by Modulating Aurora A. Mol. Biol. Cell 19: 2389-2401 [Abstract] [Full Text]  
  • Zhang, X., Ling, M.-T., Wang, Q., Lau, C.-K., Leung, S. C. L., Lee, T. K., Cheung, A. L. M., Wong, Y.-C., Wang, X. (2007). Identification of a Novel Inhibitor of Differentiation-1 (ID-1) Binding Partner, Caveolin-1, and Its Role in Epithelial-Mesenchymal Transition and Resistance to Apoptosis in Prostate Cancer Cells. J. Biol. Chem. 282: 33284-33294 [Abstract] [Full Text]  
  • O'Lone, R., Knorr, K., Jaffe, I. Z., Schaffer, M. E., Martini, P. G. V., Karas, R. H., Bienkowska, J., Mendelsohn, M. E., Hansen, U. (2007). Estrogen Receptors {alpha} and {beta} Mediate Distinct Pathways of Vascular Gene Expression, Including Genes Involved in Mitochondrial Electron Transport and Generation of Reactive Oxygen Species. Mol. Endocrinol. 21: 1281-1296 [Abstract] [Full Text]  
  • Lazorchak, A. S., Wojciechowski, J., Dai, M., Zhuang, Y. (2006). E2A Promotes the Survival of Precursor and Mature B Lymphocytes. J. Immunol. 177: 2495-2504 [Abstract] [Full Text]  
  • Renne, C., Martin-Subero, J. I., Eickernjager, M., Hansmann, M.-L., Kuppers, R., Siebert, R., Brauninger, A. (2006). Aberrant Expression of ID2, a Suppressor of B-Cell-Specific Gene Expression, in Hodgkin's Lymphoma. Am. J. Pathol. 169: 655-664 [Abstract] [Full Text]  
  • Luo, Q., Nieves, E., Kzhyshkowska, J., Angeletti, R. H. (2006). Endogenous Transforming Growth Factor-{beta} Receptor-mediated Smad Signaling Complexes Analyzed by Mass Spectrometry. Mol. Cell. Proteomics 5: 1245-1260 [Abstract] [Full Text]  
  • Ding, B., Liu, C.-j., Huang, Y., Yu, J., Kong, W., Lengyel, P. (2006). p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins. J. Biol. Chem. 281: 14893-14906 [Abstract] [Full Text]  
  • Leeanansaksiri, W., Wang, H., Gooya, J. M., Renn, K., Abshari, M., Tsai, S., Keller, J. R. (2005). IL-3 Induces Inhibitor of DNA-Binding Protein-1 in Hemopoietic Progenitor Cells and Promotes Myeloid Cell Development. J. Immunol. 174: 7014-7021 [Abstract] [Full Text]  
  • Buitenhuis, M., van Deutekom, H. W. M., Verhagen, L. P., Castor, A., Jacobsen, S. E. W., Lammers, J.-W. J., Koenderman, L., Coffer, P. J. (2005). Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2. Blood 105: 4272-4281 [Abstract] [Full Text]  
  • Light, W., Vernon, A. E., Lasorella, A., Iavarone, A., LaBonne, C. (2005). Xenopus Id3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells. Development 132: 1831-1841 [Abstract] [Full Text]  
  • Vickers, E. R., Kasza, A., Kurnaz, I. A., Seifert, A., Zeef, L. A. H., O'Donnell, A., Hayes, A., Sharrocks, A. D. (2004). Ternary Complex Factor-Serum Response Factor Complex-Regulated Gene Activity Is Required for Cellular Proliferation and Inhibition of Apoptotic Cell Death. Mol. Cell. Biol. 24: 10340-10351 [Abstract] [Full Text]  
  • Forrest, S., McNamara, C. (2004). Id Family of Transcription Factors and Vascular Lesion Formation. Arterioscler. Thromb. Vasc. Bio. 24: 2014-2020 [Abstract] [Full Text]  
  • Hata, K., Yoshimoto, T., Mizuguchi, J. (2004). CD40 Ligand Rescues Inhibitor of Differentiation 3-Mediated G1 Arrest Induced by Anti-IgM in WEHI-231 B Lymphoma Cells. J. Immunol. 173: 2453-2461 [Abstract] [Full Text]  
  • Murphy, D. J., Swigart, L. B., Israel, M. A., Evan, G. I. (2004). Id2 Is Dispensable for Myc-Induced Epidermal Neoplasia. Mol. Cell. Biol. 24: 2083-2090 [Abstract] [Full Text]  
  • Costamagna, E., Garcia, B., Santisteban, P. (2004). The Functional Interaction between the Paired Domain Transcription Factor Pax8 and Smad3 Is Involved in Transforming Growth Factor-{beta} Repression of the Sodium/Iodide Symporter Gene. J. Biol. Chem. 279: 3439-3446 [Abstract] [Full Text]  
  • O'Toole, P. J., Inoue, T., Emerson, L., Morrison, I. E. G., Mackie, A. R., Cherry, R. J., Norton, J. D. (2003). Id Proteins Negatively Regulate Basic Helix-Loop-Helix Transcription Factor Function by Disrupting Subnuclear Compartmentalization. J. Biol. Chem. 278: 45770-45776 [Abstract] [Full Text]  
  • Gonda, H., Sugai, M., Nambu, Y., Katakai, T., Agata, Y., Mori, K. J., Yokota, Y., Shimizu, A. (2003). The Balance Between Pax5 and Id2 Activities Is the Key to AID Gene Expression. JEM 198: 1427-1437 [Abstract] [Full Text]  
  • Stinson, J., Inoue, T., Yates, P., Clancy, A., Norton, J. D., Sharrocks, A. D. (2003). Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs. Nucleic Acids Res 31: 4717-4728 [Abstract] [Full Text]  
  • Alway, S. E., Degens, H., Krishnamurthy, G., Chaudhrai, A. (2003). Denervation Stimulates Apoptosis But Not Id2 Expression in Hindlimb Muscles of Aged Rats. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58: B687-697 [Abstract] [Full Text]  
  • Wilson, J. W., Deed, R. W., Inoue, T., Balzi, M., Becciolini, A., Faraoni, P., Potten, C. S., Norton, J. D. (2001). Expression of Id Helix-Loop-Helix Proteins in Colorectal Adenocarcinoma Correlates with p53 Expression and Mitotic Index. Cancer Res. 61: 8803-8810 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»