This Article
Right arrow Full Text
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 Kim, S.-W.
Right arrow Articles by Lee, H.-W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, S.-W.
Right arrow Articles by Lee, H.-W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2002, p. 8409-8414, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8409-8414.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Multiple Developmental Defects Derived from Impaired Recruitment of ASC-2 to Nuclear Receptors in Mice: Implication for Posterior Lenticonus with Cataract

Seung-Whan Kim,1 Cheolho Cheong,2,3 Young-Chang Sohn,1 Young-Hwa Goo,1 Wan Je Oh,3 Jung Hwan Park,3 So Young Joe,3,4 Hyen-Sam Kang,2 Duk-Kyung Kim,3,4,5 Changwon Kee,3,4,6 Jae Woon Lee,1* and Han-Woong Lee3,4,7*

Department of Life Science, Pohang University of Science and Technology, Pohang 790-784,1 School of Biological Sciences and Department of Microbiology, Seoul National University, Seoul 151-742,2 Samsung Biomedical Research Institute,3 Molecular Therapy Research Center, Samsung Medical Center, Seoul 135-710,5 Department of Medicine,6 Department of Ophthalmology,7 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea4

Received 19 April 2002/ Returned for modification 2 August 2002/ Accepted 17 September 2002

ASC-2, a recently isolated transcriptional coactivator molecule, stimulates transactivation by multiple transcription factors, including nuclear receptors. We generated a potent dominant negative fragment of ASC-2, encompassing the N-terminal LXXLL motif that binds a broad range of nuclear receptors. This fragment, termed DN1, specifically inhibited endogenous ASC-2 from binding these receptors in vivo, whereas DN1/m, in which the LXXLL motif was mutated to LXXAA to abolish the receptor interactions, was inert. Interestingly, DN1 transgenic mice but not DN1/m transgenic mice exhibited severe microphthalmia and posterior lenticonus with cataract as well as a variety of pathophysiological phenotypes in many other organs. Our results provide a novel insight into the molecular and histopathological mechanism of posterior lenticonus with cataract and attest to the importance of ASC-2 as a pivotal transcriptional coactivator of nuclear receptors in vivo.

* Corresponding author. Mailing address for Han-Woong Lee: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea. Phone: 82 31 299 6135. Fax: 82 31 299 6435. E-mail: hwl{at}skku.ac.kr. Mailing address: Jae Woon Lee, Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea. Phone: 82 54 279 2129. Fax: 82 54 279 8374. E-mail: jaewoon{at}postech.ac.kr.

Molecular and Cellular Biology, December 2002, p. 8409-8414, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8409-8414.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kim, G. H., Park, K., Yeom, S.-Y., Lee, K. J., Kim, G., Ko, J., Rhee, D.-K., Kim, Y. H., Lee, H. K., Kim, H. W., Oh, G. T., Lee, K.-U., Lee, J. W., Kim, S.-W. (2009). Characterization of ASC-2 as an Antiatherogenic Transcriptional Coactivator of Liver X Receptors in Macrophages. Mol. Endocrinol. 23: 966-974 [Abstract] [Full Text]  
  • Lee, J., Kim, D.-H., Lee, S., Yang, Q.-H., Lee, D. K., Lee, S.-K., Roeder, R. G., Lee, J. W. (2009). A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4. Proc. Natl. Acad. Sci. USA 106: 8513-8518 [Abstract] [Full Text]  
  • Davis, J., Davis, D., Norman, B., Piatigorsky, J. (2008). Gene Expression of the Mouse Corneal Crystallin Aldh3a1: Activation by Pax6, Oct1, and p300. IOVS 49: 1814-1826 [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]  
  • Lee, S., Lee, D.-K., Dou, Y., Lee, J., Lee, B., Kwak, E., Kong, Y.-Y., Lee, S.-K., Roeder, R. G., Lee, J. W. (2006). Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases. Proc. Natl. Acad. Sci. USA 103: 15392-15397 [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]  
  • 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]  
  • Hultman, M. L., Krasnoperova, N. V., Li, S., Du, S., Xia, C., Dietz, J. D., Lala, D. S., Welsch, D. J., Hu, X. (2005). The Ligand-Dependent Interaction of Mineralocorticoid Receptor with Coactivator and Corepressor Peptides Suggests Multiple Activation Mechanisms. Mol. Endocrinol. 19: 1460-1473 [Abstract] [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]  
  • Li, X., O'Malley, B. W. (2003). Unfolding the Action of Progesterone Receptors. J. Biol. Chem. 278: 39261-39264 [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]  
  • 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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»