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BIOCHEMISTRY
 
 

Dr. Hung-Ying Kao

Associate Professor

Pub Med:

Dr. Hung-Ying Kao

The ultimate goal of my research is to understand the mechanisms of the transcriptional control by diverse signaling pathways and the molecular basis of human diseases related to transcriptional regulation. One of the approaches toward these goals is using nuclear hormone receptors as a model system. Another major focus of my research is to characterize the biochemical properties and to determine the physiological role of the newly identified class II histone deacetylases.

Nuclear hormone receptors are cellular effectors for lipophilic hormones that ultimately regulate cell differentiation, proliferation, and animal development. Our understanding of the mechanism of transcriptional regulation by nuclear hormone receptors has been greatly advanced due to the isolation and characterization of the transcriptional co-factors including co-activators and co-repressors. SMRT and N-CoR were originally isolated as nuclear receptor-interacting factors that bind nuclear receptors in a hormone-sensitive manner. Both factors are large platform proteins and contain multiple repression domains. In addition to nuclear hormone signaling, SMRT/N-CoR have been implicated in diverse signaling pathways. Initial characterization of SMRT-interacting factors from a yeast two-hybrid screen suggested that some of these interacting partners possess enzymatic activities that might contribute or regulate SMRT functions. We will continue to characterize these factors and examine their roles in SMRT functions.

Reversible histone modification such as acetylation plays a pivotal role in chromatin remodeling and regulation of gene expression. The acetylation state of core histones is controlled by the interplay between histone acetyltransferases (HATs) and deacetylases (HDACs). Class II deacetylases HDAC5 and HDAC7 were identified as factors that mediate SMRT repression activity. These deacetylases have distinct tissue expression patterns and are structurally divergent from class I deacetylase such as HDAC1. Recent reports suggested that HDAC5 plays a role in muscle differentiation by regulating the activity of myogenic enhacer factor 2 (MEF2). We will use combination techniques of biochemistry , genetics, and molecular biology to identify what other signaling pathways class II HDACs participate in and to determine their roles in cell differentiation and proliferation.

Selected References

  • Chengzhuo Gao, Xiwen Cheng, Minh Lam, Yu Liu1, Qing Liu, Kun-Sang Chang, and Hung-Ying Kao. Signal-dependent regulation of transcription by histone deacetylase 7 (HDAC7) involves recruitment to PML nuclear bodies. 2008, Mol Biol Cell. 2008 Jul;19(7):3020-7.
  • Kris Stanya, Yu Liu, Anthony Means, and Hung-Ying Kao Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT  2008 J. Cell Biology (in press).
  • Chengzhuo Gao, Chun-Chen Ho, Erin Reineke, Minh Lam, Xiwen Cheng, Kris Stanya, Yu Liu, Sharmistha Chakraborty, Hsiu-Ming Shih, Hung-Ying Kao. Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body (NB) formation. 2008 Mol Cell Biol. (in press)
  • Hang Hoon Ha, Bong Sook Jhun, Hung-Ying Kao, and Zheng-Gen Jin. VEGF stimulates HDAC7 phosphorylation and nuclear export to mediate expression of matrix metalloproteinase and angiogenesis. 2008 Ateriosclerosis, Thrombosis, and Vascular Biology (in press).
  • Masanori Nojima, Yehong Huang, Mudit Tyagi, Hung-Ying Kao, and Koh Fujinaga The positive transcription elongation factor b is an essential co-factor for the activation of transcription by myocyte enhancer factor 2. Journal of Molecular Biology (in press).

  • Erin L. Reineke, Minh Lam, Qing Liu, Yu Liu, Kristopher J. Stanya, Kun-Sang Chang, Anthony R. Means and Hung-Ying Kao. Degradation of the tumor suppressor PML by Pin1 contributes to the cancer phenotype of breast cancer MDA-MB-231 cells. Mol Cell Biol. 2008 Feb;28(3):997-1006.

  • Erin L. Reineke, Heng Liu, Minh Lam, Yu Liu, and Hung-Ying Kao. Aberrant association of PML-RAR? with co-activators contributes its ability to regulate gene expression. J Biol Chem. 2007 Jun 22;282(25):18584-96.

  • Sharmistha Chakraborty, Xiwen Cheng, Minh Lam#, Erin L. Reineke, Xiaofang Li++, Yu Liu, Chengzhuo Gao, Simran Khurana, and Hung-Ying Kao Alpha actinin 4 potentiates MEF2 transcription activity by antagonizing histone deacetylase 7. J Biol. Chem. 2006 281(46):35070-35080.

  • Chengzhuo Gao, Xiaofang Li++, Minh Lam#, Yu Liu, Sharmistha Charkraborty, and Hung-Ying Kao. CRM1 promotes HDAC7 nuclear export independent of HDAC7 phosphorylation and its association with 14-3-3s. FEBS LETTERS 2006 580: 5096-5104.

  • Heng Liu, Chong-Kuang Shaw, Erin L. Reineke, Yu Liu, and Hung-Ying Kao. RXR? helix 12 plays an inhibitory role in the recruitment of the p160 co-activators by unliganded RXR?/RAR? heterodimers. J Biol. Chem. 2004 Oct 22;279(43):45208-18.

  • Xiaofang Li, Song Song, Yu Liu, Sung-Hawn Ko, and Hung-Ying KaoPhosphorylation of the histone deacetylase 7 modulates its stability and association with 14-3-3 proteins. (2004) J Biol Chem. 279(33):34201-8.

  • Tsai, C.-C., Kao, H.-Y., Banayo, E., Thaler, J., and Evans, R. M. Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4047-52.

  • Xiao, H, Chung J., Silva D., Kao H.-Y., Yang Y.-C. Tip60 Is a Co-repressor for STAT3. (2003). J Biol Chem 278(13):11197-204

  • Hung-Ying Kao, Chris C. Han, Anton Komar, and Ronald M. Evans. Co- repressor release, but not ligand binding, is a pre-requisite for transcription activation by human RAR? ligand binding domain (2003).J. Bio. Chem. 278: 7366-7373. (corresponding author).

  • Lemercier, C. Brocard, M.-P., Puvion-Dutilleul, F., Kao, H.-Y., Albagli, O., Khochbin, S. (2002) Class II HDACs are directly recruited by the (BTB)POZ/zinc finger BCL6 transcriptional repressor. J. Bio. Chem. 277(24):22045-52.

  • Hung-Ying Kao, Chih-Hao Lee, Andrei Komarov, Chris C. Han, and Evans, R. M. (2002) Isolation and characterization of HDAC10, a novel histone deacetylase. J. Bio. Chem. 277: 183-197. (corresponding author).

  • Hung-Ying Kao, André Verdel, Chih-Cheng Tsai, Cynthia Simon, Henry Juguilon, and Saadi Kchobin. (2001) Mechanism for nucleocytoplasmic shuttling of HDAC7. J. Bio. Chem. 276: 47496-47507. (corresponding author).

  • Khochbin Saadi and Hung-Ying Kao. (2001) Histone deacetylase complexes : functional entities or molecular reservoirs. FEBS Letters494: 141-144.