A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

doi:10.1128/MCB.20.14.5048-5063.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Mahajan, M. A.
	Articles by Samuels, H. H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Mahajan, M. A.
	Articles by Samuels, H. H.

Previous Article | Next Article

Molecular and Cellular Biology, July 2000, p. 5048-5063, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

Muktar A. Mahajan and Herbert H. Samuels^*

Division of Clinical and Molecular Endocrinology, Department of Medicine, and Department of Pharmacology, New York University School of Medicine, New York, New York 10016

Received 18 February 2000/Returned for modification 4 April 2000/Accepted 14 April 2000

We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the functionof nuclear hormone receptors in a ligand-dependent manner. NRCsare expressed as alternatively spliced isoforms which may exhibitdifferent intrinsic activities and receptor specificities. TheNRCs are organized into several modular structures and containa single functional LXXLL motif which associates with membersof the steroid hormone and thyroid hormone/retinoid receptor subfamilieswith high affinity. Human NRC (hNRC) harbors a potent N-terminalactivation domain (AD1), which is as active as the herpesvirusVP16 activation domain, and a second activation domain (AD2) whichoverlaps with the receptor-interacting LXXLL region. The C-terminalregion of hNRC appears to function as an inhibitory domain whichinfluences the overall transcriptional activity of the protein.Our results suggest that NRC binds to liganded receptors as adimer and this association leads to a structural change in NRCresulting in activation. hNRC binds CREB-binding protein (CBP)with high affinity in vivo, suggesting that hNRC may be an importantfunctional component of a CBP complex involved in mediating thetranscriptional effects of nuclear hormonereceptors.

^* Corresponding author. Mailing address: Division of Clinical and Molecular Endocrinology, Department of Medicine, and the Departmentof Pharmacology, New York University School of Medicine, 550 FirstAve., New York, NY 10016. Phone: (212) 263-6279. Fax: (212) 263-7701.E-mail: hs26{at}is9.nyu.edu.

Molecular and Cellular Biology, July 2000, p. 5048-5063, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Antonson, P., Jakobsson, T., Almlof, T., Guldevall, K., Steffensen, K. R., Gustafsson, J.-A. (2008). RAP250 Is a Coactivator in the Transforming Growth Factor {beta} Signaling Pathway That Interacts with Smad2 and Smad3. J. Biol. Chem. 283: 8995-9001 [Abstract] [Full Text]
Garapaty, S., Mahajan, M. A., Samuels, H. H. (2008). Components of the CCR4-NOT Complex Function as Nuclear Hormone Receptor Coactivators via Association with the NRC-interacting Factor NIF-1. J. Biol. Chem. 283: 6806-6816 [Abstract] [Full Text]
Li, Q., Chu, M.-J., Xu, J. (2007). Tissue- and Nuclear Receptor-Specific Function of the C-Terminal LXXLL Motif of Coactivator NCoA6/AIB3 in Mice. Mol. Cell. Biol. 27: 8073-8086 [Abstract] [Full Text]
Das, S., Schapira, M., Tomic-Canic, M., Goyanka, R., Cardozo, T., Samuels, H. H. (2007). Farnesyl Pyrophosphate Is a Novel Transcriptional Activator for a Subset of Nuclear Hormone Receptors. Mol. Endocrinol. 21: 2672-2686 [Abstract] [Full Text]
Mahajan, M. A., Murray, A., Levy, D., Samuels, H. H. (2007). Nuclear Receptor Coregulator (NRC): Mapping of the Dimerization Domain, Activation of p53 and STAT-2, and Identification of the Activation Domain AD2 Necessary for Nuclear Receptor Signaling. Mol. Endocrinol. 21: 1822-1834 [Abstract] [Full Text]
Tian, H., Mahajan, M. A., Wong, C. T., Habeos, I., Samuels, H. H. (2006). The N-Terminal A/B Domain of the Thyroid Hormone Receptor-{beta}2 Isoform Influences Ligand-Dependent Recruitment of Coactivators to the Ligand-Binding Domain. Mol. Endocrinol. 20: 2036-2051 [Abstract] [Full Text]
Yeom, S.-Y., Kim, G. H., Kim, C. H., Jung, H. D., Kim, S.-Y., Park, J.-Y., Pak, Y. K., Rhee, D.-K., Kuang, S.-Q., Xu, J., Han, D. J., Song, D.-K., Lee, J. W., Lee, K.-U., Kim, S.-W. (2006). Regulation of Insulin Secretion and {beta}-Cell Mass by Activating Signal Cointegrator 2. Mol. Cell. Biol. 26: 4553-4563 [Abstract] [Full Text]
Iwasaki, T., Takeshita, A., Miyazaki, W., Chin, W. W., Koibuchi, N. (2006). The Interaction of TR{beta}1-N Terminus with Steroid Receptor Coactivator-1 (SRC-1) Serves a Full Transcriptional Activation Function of SRC-1. Endocrinology 147: 1452-1457 [Abstract] [Full Text]
Gao, Z., He, Q., Peng, B., Chiao, P. J., Ye, J. (2006). Regulation of Nuclear Translocation of HDAC3 by I{kappa}B{alpha} Is Required for Tumor Necrosis Factor Inhibition of Peroxisome Proliferator-activated Receptor {gamma} Function. J. Biol. Chem. 281: 4540-4547 [Abstract] [Full Text]
Iwasaki, T., Koibuchi, N., Chin, W. W. (2005). Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator. Endocrinology 146: 3892-3899 [Abstract] [Full Text]
Choi, E., Lee, S., Yeom, S.-Y., Kim, G. H., Lee, J. W., Kim, S.-W. (2005). Characterization of Activating Signal Cointegrator-2 as a Novel Transcriptional Coactivator of the Xenobiotic Nuclear Receptor Constitutive Androstane Receptor. Mol. Endocrinol. 19: 1711-1719 [Abstract] [Full Text]
Mahajan, M. A., Samuels, H. H. (2005). Nuclear Hormone Receptor Coregulator: Role in Hormone Action, Metabolism, Growth, and Development. Endocr. Rev. 26: 583-597 [Abstract] [Full Text]
Zhang, H., Kuang, S.-Q., Liao, L., Zhou, S., Xu, J. (2004). Haploid Inactivation of the Amplified-in-Breast Cancer 3 Coactivator Reduces the Inhibitory Effect of Peroxisome Proliferator-Activated Receptor {gamma} and Retinoid X Receptor on Cell Proliferation and Accelerates Polyoma Middle-T Antigen-Induced Mammary Tumorigenesis in Mice. Cancer Res. 64: 7169-7177 [Abstract] [Full Text]
Qi, C., Kashireddy, P., Zhu, Y. T., Rao, S. M., Zhu, Y.-J. (2004). Null Mutation of Peroxisome Proliferator-activated Receptor-interacting Protein in Mammary Glands Causes Defective Mammopoiesis. J. Biol. Chem. 279: 33696-33701 [Abstract] [Full Text]
Jia, Y., Qi, C., Kashireddi, P., Surapureddi, S., Zhu, Y.-J., Rao, M. S., Le Roith, D., Chambon, P., Gonzalez, F. J., Reddy, J. K. (2004). Transcription Coactivator PBP, the Peroxisome Proliferator-activated Receptor (PPAR)-binding Protein, Is Required for PPAR{alpha}-regulated Gene Expression in Liver. J. Biol. Chem. 279: 24427-24434 [Abstract] [Full Text]
Reddy, J. K. (2004). Peroxisome Proliferators and Peroxisome Proliferator-Activated Receptor {alpha}: Biotic and Xenobiotic Sensing. Am. J. Pathol. 164: 2305-2321 [Full Text]
Goo, Y.-H., Na, S.-Y., Zhang, H., Xu, J., Hong, S., Cheong, J., Lee, S.-K., Lee, J. W. (2004). Interactions between Activating Signal Cointegrator-2 and the Tumor Suppressor Retinoblastoma in Androgen Receptor Transactivation. J. Biol. Chem. 279: 7131-7135 [Abstract] [Full Text]
Auboeuf, D., Dowhan, D. H., Li, X., Larkin, K., Ko, L., Berget, S. M., O'Malley, B. W. (2004). CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing. Mol. Cell. Biol. 24: 442-453 [Abstract] [Full Text]
Qi, C., Surapureddi, S., Zhu, Y.-J., Yu, S., Kashireddy, P., Rao, M. S., Reddy, J. K. (2003). Transcriptional Coactivator PRIP, the Peroxisome Proliferator-activated Receptor {gamma} (PPAR{gamma})-interacting Protein, Is Required for PPAR{gamma}-mediated Adipogenesis. J. Biol. Chem. 278: 25281-25284 [Abstract] [Full Text]
Schapira, M., Raaka, B. M., Das, S., Fan, L., Totrov, M., Zhou, Z., Wilson, S. R., Abagyan, R., Samuels, H. H. (2003). Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking. Proc. Natl. Acad. Sci. USA 100: 7354-7359 [Abstract] [Full Text]
Kim, S.-W., Park, K., Kwak, E., Choi, E., Lee, S., Ham, J., Kang, H., Kim, J. M., Hwang, S. Y., Kong, Y.-Y., Lee, K., Lee, J. W. (2003). Activating Signal Cointegrator 2 Required for Liver Lipid Metabolism Mediated by Liver X Receptors in Mice. Mol. Cell. Biol. 23: 3583-3592 [Abstract] [Full Text]
Zhang, H., Liao, L., Kuang, S.-Q., Xu, J. (2003). Spatial Distribution of the Messenger Ribonucleic Acid and Protein of the Nuclear Receptor Coactivator, Amplified in Breast Cancer-3, in Mice. Endocrinology 144: 1435-1443 [Abstract] [Full Text]
Antonson, P., Schuster, G. U., Wang, L., Rozell, B., Holter, E., Flodby, P., Treuter, E., Holmgren, L., Gustafsson, J.-A. (2003). Inactivation of the Nuclear Receptor Coactivator RAP250 in Mice Results in Placental Vascular Dysfunction. Mol. Cell. Biol. 23: 1260-1268 [Abstract] [Full Text]
Zhu, Y.-J., Crawford, S. E., Stellmach, V., Dwivedi, R. S., Rao, M. S., Gonzalez, F. J., Qi, C., Reddy, J. K. (2003). Coactivator PRIP, the Peroxisome Proliferator-activated Receptor-interacting Protein, Is a Modulator of Placental, Cardiac, Hepatic, and Embryonic Development. J. Biol. Chem. 278: 1986-1990 [Abstract] [Full Text]
Goo, Y.-H., Sohn, Y. C., Kim, D.-H., Kim, S.-W., Kang, M.-J., Jung, D.-J., Kwak, E., Barlev, N. A., Berger, S. L., Chow, V. T., Roeder, R. G., Azorsa, D. O., Meltzer, P. S., Suh, P.-G., Song, E. J., Lee, K.-J., Lee, Y. C., Lee, J. W. (2003). Activating Signal Cointegrator 2 Belongs to a Novel Steady-State Complex That Contains a Subset of Trithorax Group Proteins. Mol. Cell. Biol. 23: 140-149 [Abstract] [Full Text]
Kim, S.-W., Cheong, C., Sohn, Y.-C., Goo, Y.-H., Oh, W. J., Park, J. H., Joe, S. Y., Kang, H.-S., Kim, D.-K., Kee, C., Lee, J. W., Lee, H.-W. (2002). Multiple Developmental Defects Derived from Impaired Recruitment of ASC-2 to Nuclear Receptors in Mice: Implication for Posterior Lenticonus with Cataract. Mol. Cell. Biol. 22: 8409-8414 [Abstract] [Full Text]
Misra, P., Owuor, E. D., Li, W., Yu, S., Qi, C., Meyer, K., Zhu, Y.-J., Rao, M. S., Kong, A.-N. T., Reddy, J. K. (2002). Phosphorylation of Transcriptional Coactivator Peroxisome Proliferator-activated Receptor (PPAR)-binding Protein (PBP). STIMULATION OF TRANSCRIPTIONAL REGULATION BY MITOGEN-ACTIVATED PROTEIN KINASE. J. Biol. Chem. 277: 48745-48754 [Abstract] [Full Text]
Kuang, S.-Q., Liao, L., Zhang, H., Pereira, F. A., Yuan, Y., DeMayo, F. J., Ko, L., Xu, J. (2002). Deletion of the Cancer-amplified Coactivator AIB3 Results in Defective Placentation and Embryonic Lethality. J. Biol. Chem. 277: 45356-45360 [Abstract] [Full Text]
Mahajan, S. S., Little, M. M., Vazquez, R., Wilson, A. C. (2002). Interaction of HCF-1 with a Cellular Nuclear Export Factor. J. Biol. Chem. 277: 44292-44299 [Abstract] [Full Text]
Mahajan, M. A., Murray, A., Samuels, H. H. (2002). NRC-Interacting Factor 1 Is a Novel Cotransducer That Interacts with and Regulates the Activity of the Nuclear Hormone Receptor Coactivator NRC. Mol. Cell. Biol. 22: 6883-6894 [Abstract] [Full Text]
Qi, C., Chang, J., Zhu, Y., Yeldandi, A. V., Rao, S. M., Zhu, Y.-J. (2002). Identification of Protein Arginine Methyltransferase 2 as a Coactivator for Estrogen Receptor alpha. J. Biol. Chem. 277: 28624-28630 [Abstract] [Full Text]
Misra, P., Qi, C., Yu, S., Shah, S. H., Cao, W.-Q., Rao, M. S., Thimmapaya, B., Zhu, Y., Reddy, J. K. (2002). Interaction of PIMT with Transcriptional Coactivators CBP, p300, and PBP Differential Role in Transcriptional Regulation. J. Biol. Chem. 277: 20011-20019 [Abstract] [Full Text]
Ko, L., Cardona, G. R., Henrion-Caude, A., Chin, W. W. (2002). Identification and Characterization of a Tissue-Specific Coactivator, GT198, That Interacts with the DNA-Binding Domains of Nuclear Receptors. Mol. Cell. Biol. 22: 357-369 [Abstract] [Full Text]
Ko, L., Cardona, G. R., Iwasaki, T., Bramlett, K. S., Burris, T. P., Chin, W. W. (2002). Ser-884 Adjacent to the LXXLL Motif of Coactivator TRBP Defines Selectivity for ERs and TRs. Mol. Endocrinol. 16: 128-140 [Abstract] [Full Text]
Li, D., Wang, F., Samuels, H. H. (2001). Domain Structure of the NRIF3 Family of Coregulators Suggests Potential Dual Roles in Transcriptional Regulation. Mol. Cell. Biol. 21: 8371-8384 [Abstract] [Full Text]
Gaughan, L., Brady, M. E., Cook, S., Neal, D. E., Robson, C. N. (2001). Tip60 Is a Co-activator Specific for Class I Nuclear Hormone Receptors. J. Biol. Chem. 276: 46841-46848 [Abstract] [Full Text]
Sohn, Y. C., Kwak, E., Na, Y., Lee, J. W., Lee, S.-K. (2001). Silencing Mediator of Retinoid and Thyroid Hormone Receptors and Activating Signal Cointegrator-2 as Transcriptional Coregulators of the Orphan Nuclear Receptor Nur77. J. Biol. Chem. 276: 43734-43739 [Abstract] [Full Text]
Zhu, Y., Qi, C., Cao, W.-Q., Yeldandi, A. V., Sambasiva Rao, M., Reddy, J. K. (2001). Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function. Proc. Natl. Acad. Sci. USA 10.1073/pnas.181347498v1 [Abstract] [Full Text]
Mak, H. Y., Parker, M. G. (2001). Use of Suppressor Mutants To Probe the Function of Estrogen Receptor-p160 Coactivator Interactions. Mol. Cell. Biol. 21: 4379-4390 [Abstract] [Full Text]
Mathur, M., Tucker, P. W., Samuels, H. H. (2001). PSF Is a Novel Corepressor That Mediates Its Effect through Sin3A and the DNA Binding Domain of Nuclear Hormone Receptors. Mol. Cell. Biol. 21: 2298-2311 [Abstract] [Full Text]
Heery, D. M., Hoare, S., Hussain, S., Parker, M. G., Sheppard, H. (2001). Core LXXLL Motif Sequences in CREB-binding Protein, SRC1, and RIP140 Define Affinity and Selectivity for Steroid and Retinoid Receptors. J. Biol. Chem. 276: 6695-6702 [Abstract] [Full Text]
Iwasaki, T., Chin, W. W., Ko, L. (2001). Identification and Characterization of RRM-containing Coactivator Activator (CoAA) as TRBP-interacting Protein, and Its Splice Variant as a Coactivator Modulator (CoAM). J. Biol. Chem. 276: 33375-33383 [Abstract] [Full Text]
Zhu, Y., Qi, C., Cao, W.-Q., Yeldandi, A. V., Rao, M. S., Reddy, J. K. (2001). Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function. Proc. Natl. Acad. Sci. USA 98: 10380-10385 [Abstract] [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals