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Molecular Endocrinology, Vol 10, 813-825, Copyright © 1996 by Endocrine Society

ARTICLES

Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors

S Sande and ML Privalsky
Section of Microbiology, University of California at Davis 95616, USA.

Nuclear hormone receptors are the largest known family of eukaryotic transcription factors and serve as critical effectors of vertebrate homeostasis, growth, and differentiation. The precise transcriptional response mediated by a given nuclear hormone receptor is dictated by hormone, promoter, and cellular context, and many nuclear hormone receptors function bimodally as both transcriptional activators and repressors. We report here the identification of a family of proteins, denoted TRACs (T3 receptor-associating cofactors), which physically interact with nuclear hormone receptors and can modulate the transcriptional properties of these receptors. TRACs associate with retinoic acid, retinoid X, and thyroid hormone receptors, as well as the PML-RAR alpha and v-Erb A oncoproteins. Certain TRAC forms attenuate target gene expression and may serve as corepressors, whereas other TRAC family members appear to counteract these effects. We suggest that TRACs and related cofactors may participate in dictating the pleiotropic transcriptional capacities of the nuclear hormone receptors.


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S.-H. Hong, C.-W. Wong, and M. L. Privalsky
Signaling by Tyrosine Kinases Negatively Regulates the Interaction between Transcription Factors and SMRT (Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor) Corepressor
Mol. Endocrinol., August 1, 1998; 12(8): 1161 - 1171.
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C. Rachez, Z. Suldan, J. Ward, C.-P. B. Chang, D. Burakov, H. Erdjument-Bromage, P. Tempst, and L. P. Freedman
A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system
Genes & Dev., June 15, 1998; 12(12): 1787 - 1800.
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M. Kullmann, J. Schneikert, J. Moll, S. Heck, M. Zeiner, U. Gehring, and A. C. B. Cato
RAP46 Is a Negative Regulator of Glucocorticoid Receptor Action and Hormone-induced Apoptosis
J. Biol. Chem., June 5, 1998; 273(23): 14620 - 14625.
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E. Treuter, T. Albrektsen, L. Johansson, J. Leers, and J.-A. Gustafsson
A Regulatory Role for RIP140 in Nuclear Receptor Activation
Mol. Endocrinol., June 1, 1998; 12(6): 864 - 881.
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R. J. Clifton-Bligh, F. de Zegher, R. L. Wagner, T. N. Collingwood, I. Francois, M. Van Helvoirt, R. J. Fletterick, and V. K. K. Chatterjee
A Novel TR{beta} Mutation (R383H) in Resistance to Thyroid Hormone Syndrome Predominantly Impairs Corepressor Release and Negative Transcriptional Regulation
Mol. Endocrinol., May 1, 1998; 12(5): 609 - 621.
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X. Zhang, M. Jeyakumar, S. Petukhov, and M. K. Bagchi
A Nuclear Receptor Corepressor Modulates Transcriptional Activity of Antagonist-Occupied Steroid Hormone Receptor
Mol. Endocrinol., April 1, 1998; 12(4): 513 - 524.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
M. L. Privalsky
Depudecin makes a debut
PNAS, March 31, 1998; 95(7): 3335 - 3337.
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H. Li and J. D. Chen
The Receptor-associated Coactivator 3 Activates Transcription through CREB-binding Protein Recruitment and Autoregulation
J. Biol. Chem., March 6, 1998; 273(10): 5948 - 5954.
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L. J. Burke, M. Downes, V. Laudet, and G. E. O. Muscat
Identification and Characterization of a Novel Corepressor Interaction Region in RVR and Rev-erbA{alpha}
Mol. Endocrinol., February 1, 1998; 12(2): 248 - 262.
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 EndocrinologyHome page
T. Tagami and J. L. Jameson
Nuclear Corepressors Enhance the Dominant Negative Activity of Mutant Receptors That Cause Resistance to Thyroid Hormone
Endocrinology, February 1, 1998; 139(2): 640 - 650.
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 Proc. Natl. Acad. Sci. USAHome page
I. Zamir, J. Dawson, R. M. Lavinsky, C. K. Glass, M. G. Rosenfeld, and M. A. Lazar
Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex
PNAS, December 23, 1997; 94(26): 14400 - 14405.
[Abstract] [Full Text] [PDF]

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H. Li, C. Leo, D. J. Schroen, and J. D. Chen
Characterization of Receptor Interaction and Transcriptional Repression by the Corepressor SMRT
Mol. Endocrinol., December 1, 1997; 11(13): 2025 - 2037.
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 EndocrinologyHome page
K.-h. Lin, X.-G. Zhu, H.-C. Hsu, S.-L. Chen, H.-y. Shieh, S.-T. Chen, P. McPhie, and S.-y. Cheng
Dominant Negative Activity of Mutant Thyroid Hormone {alpha}1 Receptors from Patients with Hepatocellular Carcinoma
Endocrinology, December 1, 1997; 138(12): 5308 - 5315.
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S. Kersten, P. R. Reczek, and N. Noy
The Tetramerization Region of the Retinoid X Receptor Is Important for Transcriptional Activation by the Receptor
J. Biol. Chem., November 21, 1997; 272(47): 29759 - 29768.
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T. Monden, F. E. Wondisford, and A. N. Hollenberg
Isolation and Characterization of a Novel Ligand-dependent Thyroid Hormone Receptor-coactivating Protein
J. Biol. Chem., November 21, 1997; 272(47): 29834 - 29841.
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M. K. Bhat, C.-l. Yu, N. Yap, Q. Zhan, Y. Hayashi, P. Seth, and S.-y. Cheng
Tumor Suppressor p53 Is a Negative Regulator in Thyroid Hormone Receptor Signaling Pathways
J. Biol. Chem., November 14, 1997; 272(46): 28989 - 28993.
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 Mol. Endocrinol.Home page
R. E. M. Scott, X. S. Wu-Peng, P. M. Yen, W. W. Chin, and D. W. Pfaff
Interactions of Estrogen- and Thyroid Hormone Receptors on a Progesterone Receptor Estrogen Response Element (ERE) Sequence: a Comparison with the Vitellogenin A2 Consensus ERE
Mol. Endocrinol., October 1, 1997; 11(11): 1581 - 1592.
[Abstract] [Full Text]

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H. P. Harding, G. B. Atkins, A. B. Jaffe, W. J. Seo, and M. A. Lazar
Transcriptional Activation and Repression by ROR{alpha}, an Orphan Nuclear Receptor Required for Cerebellar Development
Mol. Endocrinol., October 1, 1997; 11(11): 1737 - 1746.
[Abstract] [Full Text]

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P. Dhordain, O. Albagli, R. J. Lin, S. Ansieau, S. Quief, A. Leutz, J.-P. Kerckaert, R. M. Evans, and D. Leprince
Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein
PNAS, September 30, 1997; 94(20): 10762 - 10767.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S.-H. Hong, G. David, C.-W. Wong, A. Dejean, and M. L. Privalsky
SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha  (RARalpha ) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia
PNAS, August 19, 1997; 94(17): 9028 - 9033.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
C. L. Smith, Z. Nawaz, and B. W. O’Malley
Coactivator and Corepressor Regulation of the Agonist/Antagonist Activity of the Mixed Antiestrogen, 4-Hydroxytamoxifen
Mol. Endocrinol., June 1, 1997; 11(6): 657 - 666.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
M. Söderström, A. Vo, T. Heinzel, R. M. Lavinsky, W.-M. Yang, E. Seto, D. A. Peterson, M. G. Rosenfeld, and C. K. Glass
Differential Effects of Nuclear Receptor Corepressor (N-CoR) Expression Levels on Retinoic Acid Receptor-Mediated Repression Support the Existence of Dynamically Regulated Corepressor Complexes
Mol. Endocrinol., June 1, 1997; 11(6): 682 - 692.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
H. Shibata, Z. Nawaz, S. Y. Tsai, B. W. O’Malley, and M.-J. Tsai
Gene Silencing by Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI) Is Mediated by Transcriptional Corepressors, Nuclear Receptor-Corepressor (N-CoR) and Silencing Mediator for Retinoic Acid Receptor and Thyroid Hormone Receptor (SMRT)
Mol. Endocrinol., June 1, 1997; 11(6): 714 - 724.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
M. Jeyakumar, M. R. Tanen, and M. K. Bagchi
Analysis of the Functional Role of Steroid Receptor Coactivator-1 in Ligand-Induced Transactivation by Thyroid Hormone Receptor
Mol. Endocrinol., June 1, 1997; 11(6): 755 - 767.
[Abstract] [Full Text]

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S. Kersten, H. Gronemeyer, and N. Noy
The DNA Binding Pattern of the Retinoid X Receptor Is Regulated by Ligand-dependent Modulation of Its Oligomeric State
J. Biol. Chem., May 9, 1997; 272(19): 12771 - 12777.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
S. M. Yoh, V. K. K. Chatterjee, and M. L. Privalsky
Thyroid Hormone Resistance Syndrome Manifests as an Aberrant Interaction between Mutant T3 Receptors and Transcriptional Corepressors
Mol. Endocrinol., April 1, 1997; 11(4): 470 - 480.
[Abstract] [Full Text]

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I Zamir, J Zhang, and M A Lazar
Stoichiometric and steric principles governing repression by nuclear hormone receptors.
Genes & Dev., April 1, 1997; 11(7): 835 - 846.
[Abstract] [PDF]

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G. B. Tremblay, A. Tremblay, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, F. Labrie, and V. Giguère
Cloning, Chromosomal Localization, and Functional Analysis of the Murine Estrogen Receptor {beta}
Mol. Endocrinol., March 1, 1997; 11(3): 353 - 365.
[Abstract] [Full Text]

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Y.-T. Ting, M. Bhat, R. Wong, and S.-y. Cheng
Tissue-specific Stabilization of the Thyroid Hormone beta 1 Nuclear Receptor by Phosphorylation
J. Biol. Chem., February 14, 1997; 272(7): 4129 - 4134.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. N. Hollenberg, T. Monden, J. P. Madura, K. Lee, and F. E. Wondisford
Function of Nuclear Co-repressor Protein on Thyroid Hormone Response Elements Is Regulated by the Receptor A/B Domain
J. Biol. Chem., November 8, 1996; 271(45): 28516 - 28520.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. M. Yoh and M. L. Privalsky
Transcriptional Repression by Thyroid Hormone Receptors. A ROLE FOR RECEPTOR HOMODIMERS IN THE RECRUITMENT OF SMRT COREPRESSOR
J. Biol. Chem., May 11, 2001; 276(20): 16857 - 16867.
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X. Feng, Y. Jiang, P. Meltzer, and P. M. Yen
Transgenic Targeting of a Dominant Negative Corepressor to Liver Blocks Basal Repression by Thyroid Hormone Receptor and Increases Cell Proliferation
J. Biol. Chem., April 27, 2001; 276(18): 15066 - 15072.
[Abstract] [Full Text] [PDF]

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M. G. Rosenfeld and C. K. Glass
Coregulator Codes of Transcriptional Regulation by Nuclear Receptors
J. Biol. Chem., September 28, 2001; 276(40): 36865 - 36868.
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