| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Section of Microbiology Division of Biological Sciences University of California at Davis Davis, California 95616
Nuclear hormone receptors are hormone-regulated transcription factors that bind to specific sites on DNA and modulate the expression of adjacent target genes. Many nuclear hormone receptors display bimodal transcriptional properties; thyroid hormone receptors, for example, typically repress target gene expression in the absence of hormone, but activate target gene expression in the presence of hormone. The ability to repress is closely linked to the ability of the apo-receptor to physically bind to auxiliary corepressor proteins denoted SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor), which, in turn, help mediate the actual molecular events involved in transcriptional silencing. We report here that repression by thyroid hormone receptors can be regulated not only by cognate hormone, but also by certain tyrosine kinase signal transduction pathways, such as that represented by the epidermal growth factor-receptor. Activation of tyrosine kinase signaling leads to inhibition of T3R-mediated repression with relatively little effect on activation. These effects appear to be mediated by a kinase-initiated disruption of the ability of T3R to interact with SMRT corepressor. Intriguingly, tyrosine kinase signaling similarly disrupted the interactions of SMRT with v-Erb A, with retinoic acid receptors, and with PLZF, a nonreceptor transcriptional repressor. We conclude that tyrosine kinase signaling exerts potentially important regulatory effects on transcriptional silencing mediated by a variety of transcription factors that operate through the SMRT corepressor complex.
This article has been cited by other articles:
 |
|
 |
|
  B. A. Jonas, N. Varlakhanova, F. Hayakawa, M. Goodson, and M. L. Privalsky Response of SMRT (Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor) and N-CoR (Nuclear Receptor Corepressor) Corepressors to Mitogen-Activated Protein Kinase Kinase Kinase Cascades Is Determined by Alternative mRNA Splicing Mol. Endocrinol., August 1, 2007; 21(8): 1924 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lee and M. L. Privalsky Heterodimers of Retinoic Acid Receptors and Thyroid Hormone Receptors Display Unique Combinatorial Regulatory Properties Mol. Endocrinol., April 1, 2005; 19(4): 863 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Jonas and M. L. Privalsky SMRT and N-CoR Corepressors Are Regulated by Distinct Kinase Signaling Pathways J. Biol. Chem., December 24, 2004; 279(52): 54676 - 54686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takahashi, M. J. McConnell, H. Harigae, M. Kaku, T. Sasaki, A. M. Melnick, and J. D. Licht The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT Blood, June 15, 2004; 103(12): 4650 - 4658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Hong, Z. Yang, and M. L. Privalsky Arsenic Trioxide Is a Potent Inhibitor of the Interaction of SMRT Corepressor with Its Transcription Factor Partners, Including the PML-Retinoic Acid Receptor {alpha} Oncoprotein Found in Human Acute Promyelocytic Leukemia Mol. Cell. Biol., November 1, 2001; 21(21): 7172 - 7182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nabeyrat, S. Corroyer, V. Besnard, V. Cazals-Laville, J. Bourbon, and A. Clement Retinoic Acid Protects against Hyperoxia-Mediated Cell-Cycle Arrest of Lung Alveolar Epithelial Cells by Preserving Late G1 Cyclin Activities Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Rowan, N. Garrison, N. L. Weigel, and B. W. O'Malley 8-Bromo-Cyclic AMP Induces Phosphorylation of Two Sites in SRC-1 That Facilitate Ligand-Independent Activation of the Chicken Progesterone Receptor and Are Critical for Functional Cooperation between SRC-1 and CREB Binding Protein Mol. Cell. Biol., December 1, 2000; 20(23): 8720 - 8730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. BURKE and A. BANIAHMAD Co-repressors 2000 FASEB J, October 1, 2000; 14(13): 1876 - 1888. [Abstract] [Full Text]
|
|
|
|
|
|
S.-H. Hong and M. L. Privalsky The SMRT Corepressor Is Regulated by a MEK-1 Kinase Pathway: Inhibition of Corepressor Function Is Associated with SMRT Phosphorylation and Nuclear Export Mol. Cell. Biol., September 1, 2000; 20(17): 6612 - 6625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Huynh, W. Fischle, E. Verdin, and V. J. Bardwell BCoR, a novel corepressor involved in BCL-6 repression Genes & Dev., July 15, 2000; 14(14): 1810 - 1823. [Abstract] [Full Text]
|
|
|
|
|
|
K. Busch, B. Martin, A. Baniahmad, J. A. Martial, R. Renkawitz, and M. Muller Silencing Subdomains of v-ErbA Interact Cooperatively with Corepressors: Involvement of Helices 5/6 Mol. Endocrinol., February 1, 2000; 14(2): 201 - 211. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. Hoatlin, Y. Zhi, H. Ball, K. Silvey, A. Melnick, S. Stone, S. Arai, N. Hawe, G. Owen, A. Zelent, et al. A Novel BTB/POZ Transcriptional Repressor Protein Interacts With the Fanconi Anemia Group C Protein and PLZF Blood, December 1, 1999; 94(11): 3737 - 3747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Hong and M. L. Privalsky Retinoid Isomers Differ in the Ability to Induce Release of SMRT Corepressor from Retinoic Acid Receptor-alpha J. Biol. Chem., January 29, 1999; 274(5): 2885 - 2892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yan and A. M. Jetten Characterization of the Repressor Function of the Nuclear Orphan Receptor Retinoid Receptor-related Testis-associated Receptor/Germ Cell Nuclear Factor J. Biol. Chem., November 3, 2000; 275(45): 35077 - 35085. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
