This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-K. Articles by Lee, J. W. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-K. Articles by Lee, J. W.

Two Distinct Nuclear Receptor-Interaction Domains and CREB-Binding Protein-Dependent Transactivation Function of Activating Signal Cointegrator-2

Center for Ligand and Transcription (S.-K.L., S.-Y.J., Y.-S.K., S.Y.N. Y.C.L., J.W.L.) Department of Biology (S.-K.L.,, S.-Y.N.) and Hormone Research Center (Y.C.L., J.W.L.) Chonnam National University Kwangju 500–757, Korea

ASC-2 is a recently isolated transcriptional cointegrator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors, AP-1, nuclear factor B (NFB), serum response factor (SRF), and numerous other transcription factors. ASC-2 contained two nuclear receptor-interaction domains, both of which are dependent on the integrity of their core LXXLL sequences. Surprisingly, the C-terminal LXXLL motif specifically interacted with oxysterol receptor LXRß, whereas the N-terminal motif bound a broad range of nuclear receptors. These interactions appeared to be essential because a specific subregion of ASC-2 including the N- or C-terminal LXXLL motif acted as a potent dominant negative mutant with transactivation by appropriate nuclear receptors. In addition, the autonomous transactivation domain (AD) of ASC-2 was found to consist of three separable subregions; i.e. AD1, AD2, and AD3. In particular, AD2 and AD3 were binding sites for CREB binding protein (CBP), and CBP-neutralizing E1A repressed the autonomous transactivation function of ASC-2. Furthermore, the receptor transactivation was not enhanced by ASC-2 in the presence of E1A and significantly impaired by overexpressed AD2. From these results, we concluded that ASC-2 directly binds to nuclear receptors and recruits CBP to mediate the nuclear receptor transactivation in vivo.

This article has been cited by other articles:

				G. H. Kim, K. Park, S.-Y. Yeom, K. J. Lee, G. Kim, J. Ko, D.-K. Rhee, Y. H. Kim, H. K. Lee, H. W. Kim, et al. Characterization of ASC-2 as an Antiatherogenic Transcriptional Coactivator of Liver X Receptors in Macrophages Mol. Endocrinol., July 1, 2009; 23(7): 966 - 974. [Abstract] [Full Text] [PDF]

				S. Lee, D.-H. Kim, Y. H. Goo, Y. C. Lee, S.-K. Lee, and J. W. Lee Crucial Roles for Interactions between MLL3/4 and INI1 in Nuclear Receptor Transactivation Mol. Endocrinol., May 1, 2009; 23(5): 610 - 619. [Abstract] [Full Text] [PDF]

				J. Lee, P. K. Saha, Q.-H. Yang, S. Lee, J. Y. Park, Y. Suh, S.-K. Lee, L. Chan, R. G. Roeder, and J. W. Lee Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis PNAS, December 9, 2008; 105(49): 19229 - 19234. [Abstract] [Full Text] [PDF]

				S. Lee, J. Lee, S.-K. Lee, and J. W. Lee Activating Signal Cointegrator-2 Is an Essential Adaptor to Recruit Histone H3 Lysine 4 Methyltransferases MLL3 and MLL4 to the Liver X Receptors Mol. Endocrinol., June 1, 2008; 22(6): 1312 - 1319. [Abstract] [Full Text] [PDF]

				P. Antonson, T. Jakobsson, T. Almlof, K. Guldevall, K. R. Steffensen, and J.-A. Gustafsson RAP250 Is a Coactivator in the Transforming Growth Factor {beta} Signaling Pathway That Interacts with Smad2 and Smad3 J. Biol. Chem., April 4, 2008; 283(14): 8995 - 9001. [Abstract] [Full Text] [PDF]

				C. J Delvecchio and J. P Capone Protein kinase C {alpha} modulates liver X receptor {alpha} transactivation J. Endocrinol., April 1, 2008; 197(1): 121 - 130. [Abstract] [Full Text] [PDF]

				Q. Li, M.-J. Chu, and J. Xu Tissue- and Nuclear Receptor-Specific Function of the C-Terminal LXXLL Motif of Coactivator NCoA6/AIB3 in Mice Mol. Cell. Biol., December 1, 2007; 27(23): 8073 - 8086. [Abstract] [Full Text] [PDF]

				J. Y. Kim, O. G. Park, J. W. Lee, and Y. C. Lee One- plus Two-hybrid System, a Novel Yeast Genetic Selection for Specific Missense Mutations Disrupting Protein/Protein Interactions Mol. Cell. Proteomics, October 1, 2007; 6(10): 1727 - 1740. [Abstract] [Full Text] [PDF]

				M. A. Mahajan, A. Murray, D. Levy, and H. H. Samuels 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., August 1, 2007; 21(8): 1822 - 1834. [Abstract] [Full Text] [PDF]

				S. Talukdar and F. B. Hillgartner The mechanism mediating the activation of acetyl-coenzyme A carboxylase-{alpha} gene transcription by the liver X receptor agonist T0-901317 J. Lipid Res., November 1, 2006; 47(11): 2451 - 2461. [Abstract] [Full Text] [PDF]

				S.-Y. Yeom, G. H. Kim, C. H. Kim, H. D. Jung, S.-Y. Kim, J.-Y. Park, Y. K. Pak, D.-K. Rhee, S.-Q. Kuang, J. Xu, et al. Regulation of Insulin Secretion and {beta}-Cell Mass by Activating Signal Cointegrator 2 Mol. Cell. Biol., June 15, 2006; 26(12): 4553 - 4563. [Abstract] [Full Text] [PDF]

				E. Choi, S. Lee, S.-Y. Yeom, G. H. Kim, J. W. Lee, and S.-W. Kim Characterization of Activating Signal Cointegrator-2 as a Novel Transcriptional Coactivator of the Xenobiotic Nuclear Receptor Constitutive Androstane Receptor Mol. Endocrinol., July 1, 2005; 19(7): 1711 - 1719. [Abstract] [Full Text] [PDF]

				M. A. Mahajan and H. H. Samuels Nuclear Hormone Receptor Coregulator: Role in Hormone Action, Metabolism, Growth, and Development Endocr. Rev., June 1, 2005; 26(4): 583 - 597. [Abstract] [Full Text] [PDF]

				M. L. Hultman, N. V. Krasnoperova, S. Li, S. Du, C. Xia, J. D. Dietz, D. S. Lala, D. J. Welsch, and X. Hu The Ligand-Dependent Interaction of Mineralocorticoid Receptor with Coactivator and Corepressor Peptides Suggests Multiple Activation Mechanisms Mol. Endocrinol., June 1, 2005; 19(6): 1460 - 1473. [Abstract] [Full Text] [PDF]

				Y.-H. Goo, S.-Y. Na, H. Zhang, J. Xu, S. Hong, J. Cheong, S.-K. Lee, and J. W. Lee Interactions between Activating Signal Cointegrator-2 and the Tumor Suppressor Retinoblastoma in Androgen Receptor Transactivation J. Biol. Chem., February 20, 2004; 279(8): 7131 - 7135. [Abstract] [Full Text] [PDF]

				S. Shah, A. Hecht, R. Pestell, and S. W. Byers Trans-repression of {beta}-Catenin Activity by Nuclear Receptors J. Biol. Chem., November 28, 2003; 278(48): 48137 - 48145. [Abstract] [Full Text] [PDF]

				H. J. Kong, H. J. Yu, S. Hong, M. J. Park, Y. H. Choi, W. G. An, J. W. Lee, and J. Cheong Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation Mol. Cancer Res., November 1, 2003; 1(13): 948 - 958. [Abstract] [Full Text] [PDF]

				S.-W. Kim, K. Park, E. Kwak, E. Choi, S. Lee, J. Ham, H. Kang, J. M. Kim, S. Y. Hwang, Y.-Y. Kong, et al. Activating Signal Cointegrator 2 Required for Liver Lipid Metabolism Mediated by Liver X Receptors in Mice Mol. Cell. Biol., May 15, 2003; 23(10): 3583 - 3592. [Abstract] [Full Text] [PDF]

				P. Antonson, G. U. Schuster, L. Wang, B. Rozell, E. Holter, P. Flodby, E. Treuter, L. Holmgren, and J.-A. Gustafsson Inactivation of the Nuclear Receptor Coactivator RAP250 in Mice Results in Placental Vascular Dysfunction Mol. Cell. Biol., February 15, 2003; 23(4): 1260 - 1268. [Abstract] [Full Text] [PDF]

				A. S. Guberman, M. E. Scassa, L. E. Giono, C. L. Varone, and E. T. Canepa Inhibitory Effect of AP-1 Complex on 5-Aminolevulinate Synthase Gene Expression through Sequestration of cAMP-response Element Protein (CRE)-binding Protein (CBP) Coactivator J. Biol. Chem., January 17, 2003; 278(4): 2317 - 2326. [Abstract] [Full Text] [PDF]

				Y.-H. Goo, Y. C. Sohn, D.-H. Kim, S.-W. Kim, M.-J. Kang, D.-J. Jung, E. Kwak, N. A. Barlev, S. L. Berger, V. T. Chow, et al. Activating Signal Cointegrator 2 Belongs to a Novel Steady-State Complex That Contains a Subset of Trithorax Group Proteins Mol. Cell. Biol., January 1, 2003; 23(1): 140 - 149. [Abstract] [Full Text]

				S.-W. Kim, C. Cheong, Y.-C. Sohn, Y.-H. Goo, W. J. Oh, J. H. Park, S. Y. Joe, H.-S. Kang, D.-K. Kim, C. Kee, et al. Multiple Developmental Defects Derived from Impaired Recruitment of ASC-2 to Nuclear Receptors in Mice: Implication for Posterior Lenticonus with Cataract Mol. Cell. Biol., December 15, 2002; 22(24): 8409 - 8414. [Abstract] [Full Text] [PDF]

				Y. C. Sohn, E. Kwak, Y. Na, J. W. Lee, and S.-K. Lee 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., November 16, 2001; 276(47): 43734 - 43739. [Abstract] [Full Text] [PDF]

				D.-J. Jung, S.-Y. Na, D. S. Na, and J. W. Lee Molecular Cloning and Characterization of CAPER, a Novel Coactivator of Activating Protein-1 and Estrogen Receptors J. Biol. Chem., January 4, 2002; 277(2): 1229 - 1234. [Abstract] [Full Text] [PDF]