This Article
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 Saatcioglu, F
Right arrow Articles by Karin, M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saatcioglu, F
Right arrow Articles by Karin, M

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 June; 13(6): 3675-3685

A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).

F Saatcioglu, P Bartunek, T Deng, M Zenke and M Karin

Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.

ABSTRACT

The thyroid hormone (T3) receptor type alpha, the c-ErbA alpha proto-oncoprotein, stimulates transcription of T3-dependent promoters, interferes with AP-1 activity, and induces erythroid differentiation in a ligand-dependent manner. The v-ErbA oncoprotein does not bind hormone and has lost all of these activities. Using c-ErbA/v-ErbA chimeras, we found that a deletion of 9 amino acids, conserved among many members of the nuclear receptor superfamily, which are located at the extreme carboxy terminus of c-ErbA alpha is responsible for loss of both transactivation and transcriptional interference activities. Single, double, and triple amino acid substitutions within this region completely abolished T3-dependent transcriptional activation, interference with AP-1 activity, and decreased T3 binding by c-ErbA alpha. However, the lower T3 binding by these mutants does not fully account for the loss of transactivation and transcriptional interference, since a c-ErbA/v-ErbA chimera which was similarly reduced in T3 binding activity has retained both of these functions. Deletion of homologous residues in the retinoic acid receptor alpha (RAR alpha) resulted in a similar loss of transactivation and transcriptional interference activities. The ability of c-ErbA alpha to induce differentiation of transformed erythroblasts is also impaired by all of the mutations introduced into the conserved carboxy-terminal sequence. We conclude that this 9-amino-acid conserved region is essential for normal biological function of c-ErbA alpha and RAR alpha and possibly other T3 and RA receptors.

Mol Cell Biol. 1993 June; 13(6): 3675-3685




This article has been cited by other articles:

  • Sanchez-Pacheco, A., Martinez-Iglesias, O., Mendez-Pertuz, M., Aranda, A. (2009). Residues K128, 132, and 134 in the Thyroid Hormone Receptor-{alpha} Are Essential for Receptor Acetylation and Activity. Endocrinology 150: 5143-5152 [Abstract] [Full Text]  
  • DeLong, L. J., Bonamy, G. M. C., Fink, E. N., Allison, L. A. (2004). Nuclear Export of the Oncoprotein v-ErbA Is Mediated by Acquisition of a Viral Nuclear Export Sequence. J. Biol. Chem. 279: 15356-15367 [Abstract] [Full Text]  
  • Warnmark, A., Treuter, E., Wright, A. P. H., Gustafsson, J.-A. (2003). Activation Functions 1 and 2 of Nuclear Receptors: Molecular Strategies for Transcriptional Activation. Mol. Endocrinol. 17: 1901-1909 [Abstract] [Full Text]  
  • Berghagen, H., Ragnhildstveit, E., Krogsrud, K., Thuestad, G., Apriletti, J., Saatcioglu, F. (2002). Corepressor SMRT Functions as a Coactivator for Thyroid Hormone Receptor T3Ralpha from a Negative Hormone Response Element. J. Biol. Chem. 277: 49517-49522 [Abstract] [Full Text]  
  • Kim, J., Kim, J.-H., Lee, S.-H., Kim, D.-H., Kang, H.-Y., Bae, S.-H., Pan, Z.-Q., Seo, Y.-S. (2002). The Novel Human DNA Helicase hFBH1 Is an F-box Protein. J. Biol. Chem. 277: 24530-24537 [Abstract] [Full Text]  
  • Slagsvold, T., Kraus, I., Bentzen, T., Palvimo, J., Saatcioglu, F. (2000). Mutational Analysis of the Androgen Receptor AF-2 (Activation Function 2) Core Domain Reveals Functional and Mechanistic Differences of Conserved Residues Compared with Other Nuclear Receptors. Mol. Endocrinol. 14: 1603-1617 [Abstract] [Full Text]  
  • Ren, Y., Behre, E., Ren, Z., Zhang, J., Wang, Q., Fondell, J. D. (2000). Specific Structural Motifs Determine TRAP220 Interactions with Nuclear Hormone Receptors. Mol. Cell. Biol. 20: 5433-5446 [Abstract] [Full Text]  
  • Robyr, D., Wolffe, A. P., Wahli, W. (2000). Nuclear Hormone Receptor Coregulators In Action: Diversity For Shared Tasks. Mol. Endocrinol. 14: 329-347 [Full Text]  
  • Caira, F., Antonson, P., Pelto-Huikko, M., Treuter, E., Gustafsson, J.-A. (2000). Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator. J. Biol. Chem. 275: 5308-5317 [Abstract] [Full Text]  
  • Tagami, T., Park, Y., Jameson, J. L. (1999). Mechanisms That Mediate Negative Regulation of the Thyroid-stimulating Hormone alpha Gene by the Thyroid Hormone Receptor. J. Biol. Chem. 274: 22345-22353 [Abstract] [Full Text]  
  • Zhang, J., Fondell, J. D. (1999). Identification of Mouse TRAP100: a Transcriptional Coregulatory Factor for Thyroid Hormone and Vitamin D Receptors. Mol. Endocrinol. 13: 1130-1140 [Abstract] [Full Text]  
  • Roux, S., Terouanne, B., Couette, B., Rafestin-Oblin, M.-E., Nicolas, J.-C. (1999). Conformational Change in the Human Glucocorticoid Receptor Induced by Ligand Binding Is Altered by Mutation of Isoleucine 747 by a Threonine. J. Biol. Chem. 274: 10059-10065 [Abstract] [Full Text]  
  • Bartunek, P., Zenke, M. (1998). Retinoid X Receptor and c-erbA/Thyroid Hormone Receptor Regulate Erythroid Cell Growth and Differentiation. Mol. Endocrinol. 12: 1269-1279 [Abstract] [Full Text]  
  • Gill, R. K., Atkins, L. M., Hollis, B. W., Bell, N. H. (1998). Mapping the Domains of the Interaction of the Vitamin D Receptor and Steroid Receptor Coactivator-1. Mol. Endocrinol. 12: 57-65 [Abstract] [Full Text]  
  • Caelles, C., Gonzalez-Sancho, J. M., Munoz, A. (1997). Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 11: 3351-3364 [Abstract] [Full Text]  
  • Wilkinson, J. R., Towle, H. C. (1997). Identification and Characterization of the AF-1 Transactivation Domain of Thyroid Hormone Receptor beta 1. J. Biol. Chem. 272: 23824-23832 [Abstract] [Full Text]  
  • Willy, P J, Mangelsdorf, D J (1997). Unique requirements for retinoid-dependent transcriptional activation by the orphan receptor LXR.. Genes Dev. 11: 289-298 [Abstract]  
  • Collingwood, T. N., Rajanayagam, O., Adams, M., Wagner, R., Cavailles, V., Kalkhoven, E., Matthews, C., Nystrom, E., Stenlof, K., Lindstedt, G., Tisell, L., Fletterick, R. J., Parker, M. G., Chatterjee, V. K. K. (1997). A natural transactivation mutation in the thyroid hormone beta  receptor: Impaired interaction with putative transcriptional mediators. Proc. Natl. Acad. Sci. USA 94: 248-253 [Abstract] [Full Text]  
  • Folkers, G. E., van Heerde, E. C., van der Saag, P. T. (1995). Activation Function 1 of Retinoic Acid Receptor beta2 Is an Acidic Activator Resembling VP16. J. Biol. Chem. 270: 23552-23559 [Abstract] [Full Text]  
  • Barres, B., Lazar, M., Raff, M. (1994). A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120: 1097-1108 [Abstract]  
  • Zhang, Z., Teng, C. T. (2000). Estrogen Receptor-related Receptor alpha 1 Interacts with Coactivator and Constitutively Activates the Estrogen Response Elements of the Human Lactoferrin Gene. J. Biol. Chem. 275: 20837-20846 [Abstract] [Full Text]  
  • Slagsvold, T., Kraus, I., Fronsdal, K., Saatcioglu, F. (2001). DNA Binding-independent Transcriptional Activation by the Androgen Receptor through Triggering of Coactivators. J. Biol. Chem. 276: 31030-31036 [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»