Researchers

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Lee, Young Chul

Title

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Associate Professor

Affiliation

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 Hormone Research Center, Chonnam National University

Degree

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Ph.D., Seoul National University

Address

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 Hormone Research Center, Chonnam National University,
Kwangju 500-757

Tel

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+82-62-530-0909

Fax

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+82-62-530-0500

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yclee@chonnam.ac.kr

  

  Research Interest


            Nuclear hormone receptors (NRs) are sequence-specific and hormone (ligand)- dependent transcription factors that control cell proliferation, differentiation, and various animal physiology. Recent progresses in identifying regulatory proteins required for NR actions uncovered the existence of diverse and multiple forms of coactivator complexes, which are generally recruited to the NR-bound promoter and enhance the transcriptional rate of target genes by influencing nucleosomal structure and/or basal transcription machinery. Intriguingly, most coactivator proteins were shown to mediate not only NR actions but also activation functions of other transcriptional factors in the context of multi-protein complex. Our research purpose is aimed at delineating the molecular mechanisms by which coactivator molecules can integrate activation signals from various transcription factors including NR. To this end, we plan to pursue three projects. 

First, we will utilize biochemical purification schemes to isolate and characterize macromolecular coactivator complexes, particularly ones associated with Activating Signal Cointegrator (ASC)-1 and ASC-2. ASC-1 and ASC-2 were originally isolated as NR coactivators and recently shown to mediate the transcriptional regulation of other mitogenic transcription factors. Identification of associated components and characterization of their biochemical activities will be helpful to understand the molecular basis of their coactivator function in the transcriptional regulation. In addition, single cell-based antibody blocking technique and in vitro transcription assay system will be employed to reveal functional importance of these coactivator proteins (or complexes) in vivo. 

Second, we are trying to understand the molecular mechanism of coactivator function with the use of yeast Saccharmyces cerevisiae which is readily susceptable to genetical and biochmical manipulations. Ectopically expressed NRs show hormone-induced transactivation functions in yeast, suggesting some NR coactivators are evolutionally conserved from yeast to human. Therefore, the combined genetic and biochemical approach through yeast system should be useful for characterization of coactivator function and further probing the functional relationship between general coactivators and metazoan-specific coactivators. 

Third, we will develope a modified yeast two hybrid system that can be used to screen for specific mutations that disrupt the association of two interacting proteins. By using diverse mutant forms of a coactivator, each of which is specifically impaired in interaction with a specific partner molecule (e.g. transcription factor or associated complex protein), we should be able to address the importance and functional relevance of each interaction in the coactivator functions. 

 

  Recent Publications

  

  1. Goo YH, Sohn YC, Kim DH, Kim SW, Kang MJ, Jung DJ, Kwak E, Barlev NA, Berger SL, Chow VT, Roeder RG, Azorsa DO, Meltzer PS, Suh PG, Song EJ, Lee KJ, Lee YC, Lee JW. (2003) Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins. Mol Cell Biol. 23(1):140-149
     
  2. Jung DJ, Sung HS, Goo YH, Lee HM, Park OK, Jung SY, Lim J, Kim HJ, Lee SK, Kim TS, Lee JW and Lee YC (2002) Novel transcriptional coactivator complex containing activating signal cointegrator 1. Mol Cell Biol, (22:5203-5211)
     
  3. Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC and Kim YJ (2001) The structural and functional organization of the yeast mediator complex. J Biol Chem, 276:42003-42010
     
  4. Lee JW, Lee YC, Na SY, Jung DJ and Lee SK (2001) Transcriptional coregulators of the nuclear receptor superfamily: coactivators and corepressors. Cell Mol Life Sci, 58:289-297
     
  5. Lee, S.K., Jung, S.Y., Kim, Y.S., Na, S.Y., Lee, Y.C., and Lee, J.W. (2001)  Two Distinct Nuclear Receptor-Interaction Domains and CREB-Binding Protein-Dependent Transactivation Function of Activating Signal Cointegrator-2. Mol. Endocrinol. 15:241-254
     
  6. Park, J.M., Kim, H.S., Han, S.J., Hwang, M.S., Lee, Y.C., and Kim, Y.J. (2000) In vivo requirement of activator-specific binding targets of mediator. Mol. Cell. Biol. 20:8709-19
     
  7. Lee, J.W., Cheong, J.H., Lee, Y.C., Na, S.Y., and Lee, S.K. (2000) Dissecting the molecular mechanism of nuclear receptor action: transcription coactivators and corepressors. Exp. Mol. Med. 32:53-60
     
  8. Lee, S.-K., Kim, J.-H., Lee, Y. C., Cheong, J. H., and Lee, J. W. (2000) Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kB, and serum response factor. J. Biol. Chem. 275:12470-12474
     
  9. Lee, S.-K., Na, S.-Y., Jung, S.-Y., Jhun, B. H., Cheong, J. H., Lee, Y. C., and Lee, J. W. (2000) Activating protein-1, nuclear factor-kB, and serum response factor, as novel target molecules of the cancer-amplified transcription coactivator ASC-2. Mol. Endocrinol. 14:915-925
     
  10. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW. (1999)  A nuclear factor, ASC-2, as a cancer-amplified  transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J. Biol. Chem. 274:34283-34293
     
  11. Kim, H.J., Yi, J.Y., Sung, H.S., Moore, D.D., Jhun, B.H., Lee, Y.C., and Lee, J.W. (1999) Activating signal cointegrator 1, a novel transcriptional coactivator of nuclear receptors, and its cytosolic localization under conditions of serum starvation. Mol. Cell. Biol. 19:6323-6332
     
  12. Na, S.Y., Choi, J.E., Kim, H.J., Jhun, B.H., Lee, Y.C., and Lee, J.W. (1999) Bcl3, an IkB protein, stimulates activating protein 1 transactivation and cellular proliferation. J. Biol. Chem. 274:28491-28496
     
  13. Lee, S.-K., Anzick, S.L., Choi, J.-E., Bubendorf, L., Guan, X.-Y., Jung, Y.-K., Kallioniemi, O.-P., Kononen, J, Trent, J.M., Azorsa, D., Jhun, B.H, Cheong, J.H., Lee, Y.C., Meltzer, P., and Lee, J.W. (1999) ASC-2, a novel transcriptional coactivator of nuclear receptors abd its amplification in human cancers. J. Biol. Chem. 274:34283-34293
     
  14. Han, S.J., Lee, Y.C., Gim, B.S., Ryu, G.-H., Park, S.J., Lane, W.S., and Kim, Y.-J. (1999) Activator-specific requirement of yeast mediator proteins for RNA polymerase II transcriptional activation. Mol. Cell. Biol. 19:979-988
     
  15. Lee, Y.C., Park, J.M., Han, S.J., Min, S., and Kim, Y.-J. (1999) An activator binding module of yeast RNA polymerase II holoenzyme. Mol. Cell. Biol. 19: 2967-2976
     
  16. Lee, Y.C. and Kim, Y.-J. (1998) Requirement for a functional interaction between yeast mediator components Med6 and Srb4 in RNA polymerase II transcription. Mol. Cell. Biol. 18: 5364-5370
     
  17. Lee, Y.C., Min, S., Gim, B.S., and Kim, Y.-J. (1997) A transcriptional mediator protein that is required for many RNA polymerase II promoters and is conserved from yeast to humans. Mol. Cell. Biol. 17: 4622-4632
     
  18. Lee, Y.C., Lee, B.J., Hwang, D.S., and Kang, H.S. (1996) Purification and characterization of mitochondrial ribonuclease P from Aspergillus nidulans. Eur. J. Biohem. 235:289-296
     
  19. Lee, Y.C., Lee, B.J., and Kang, H.S. (1996) The RNA component of mitochondrial ribonuclease P from Aspergillus nidulans. Eur. J. Biohem. 235:297-303  

 

 

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