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  • Lim, In Kyoung (임인경)

    Lim, In Kyoung (임인경) MD., PhD.

    Department of Biochemistry & Molecular Biology, Ajou University School of Medicine, San 5 Woncheon-Dong, Yeongtong-Gu, Suwon, Kyunggi-Do 443-721, Korea

    Phone: +82-31-219-5051

    Fax: +82-31-219-5059

    Email: iklim@ajou.ac.kr

Current Position
    Department of Biochemistry and Molecular Biology,
    Ajou University School of Medicine, Suwon, 443-721, Korea
    (+)82-31-219-5051 (office), (+)82-31-219-5059 (Fax).
    BK21 Project (Cell Transformation and Restorations) in Ajou University School of Medicine
Research Interest
  • Mechanism of carcinogenesis
  • Regulation of Cellular Senescence
Brief Description

Laboratory of Cellular Senescence and Carcinogenesis (LCSC)

The focus of my research is to understand molecular mechanisms of carcinogenesis and cellular senescence by tumor suppressor, TIS21/BTG2 gene, in the various cellular processes, such as cancer development, aging-related diseases, cell death, and differentiation by employing mouse model system as well as cell culture analyses. Cancer research is focused on the characterizing effects of tumor suppressor gene, TIS21/BTG2, during carcinogenic processes, and cellular senescence work is focused on the characterizing basic mechanisms regulating senescence associated p-Erk1/2 (SA-pErk1/2) and actin cytoskeleton proteins, which remodels the morphology of senescent cells.

TIS21 is an early growth response gene that was first isolated from mouse SW3T3 fibroblast after treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TIS21 belongs to the antiproliferative gene family along with BTG1, BTG3, and Tob genes. Human homolog of TIS21, named, BTG2 (B cell translocation gene 2), was cloned from a cDNA library of human lymphoblastoid cells as a gene associated with DNA damage response. Expression of TIS21/BTG2 is responsive to the various DNA damaging agent such as UV, ionizing radiation, chemotherapeutic agents in addition to various growth factors and cytokines. Recently, TIS21 has been reported as a major effector of p53-dependent proliferation arrest in mouse and human fibroblasts and inhibitor of oncogenic Ras. In my laboratory, we proposed TIS21, for the first time, as a potential tumor suppressor in the thymic carcinoma and the hepatocellular carcinoma by employing SV40T antigen transgenic mouse and TIS21 knockout mouse model systems, respectively. Indeed, TIS21 inhibited cyclin E biosynthesis and cyclin B1 associated kinase activities, indicating its regulations of G1/S and G2/M phases of cell division cycle. Moreover, we also reported the effects of TIS21/BTG2 gene on the feedback regulation of cyclinB1 and FoxM1 transcription factor, the enhanced cell death via regulations of MnSOD induction and GSK3b activity in mitochondria, the enhanced degradation of c-Myc protein in response to all-trans-retinoic acid, and the inhibition of hematopoietic precursor cell proliferation in response to estradiol. The following diagram briefly explains what we have reported about the role of TIS21 in our laboratory.

Modes of anti-carcinogenic activity of TIS21

On the other hand, we also reported universal markers of cellular senescence, such as G-actin accumulation in nuclei and cytoplasmic accumulation of SA-pErk1/2. In addition to that, we could report, for the first time, the significant accumulation of reactive oxygen species in the senescent cells by using FACS analysis.


Doctor of Medicine (M.D.) Yonsei University Medical College, Seoul Korea (1978)

Master of Science (M.Sc.) Yonsei University Graduate School, Seoul Korea (1980)

Doctor of Philosophy (Ph.D.) Yonsei University Graduate School, Seoul, Korea (1983)

Prior Experience
  • 1983-1987  Chief, Laboratory of Biochemistry
    Korea Cancer Center Hospital, Korea Advanced Energy Research Institute
  • 1987-1989  Research Associate, Department of Biochemistry
     Case Western Reserve University, School of Medicine, USA
  • 1991-1993  Visiting Scientist, Department of Biological Chemistry
    University of California Los Angeles, School of Medicine, USA
  • 1989 – present Assistant Professor, Associate Professor, and Professor
    Department of Biochemistry and Molecular Biology,
    Ajou University School of Medicine
  • 1989 – 2003   Chairperson,
    Department of Biochemistry, Ajou University School of Medicine
  • 1999 – 2002 Chairperson,
    Division of Medicine, Graduate School Ajou University
  • 2002 – 2006 General Member, Korean Academy of Science and Technology (Section of Medicine and Pharmacy)
  • 2007- present Fellow, Korean Academy of Science and Technology
    (Section of Medicine and Pharmacy)
  • 2007.3-2009.2  Chairperson, Department of Medical Genetics, Ajou University School of Medicine
  • 2006. 2-present Director of BK21 research project, Ajou University School of Medicine
  • 2006.5 -2010.8 Dean, Ajou University School of Medicine
  • 2008.8- 2010.8 Dean, Ajou University Graduate School of Medicine
  • 2007.5-2010.8 Director of Medical Education, Korean Association of Medical College
  • 2009.1-2009.12 Chairperson, The Korean Society for Gerontology
  • 2010.5-2012. 5 President, Federation of Korean Gerontological Societies
Publications(Recent 5 years)
Selected Publications
  • TIS21/BTG2/PC3 enhances downregulation of c-Myc during differentiation of HL-60 cells by activating Erk1/2 and inhibiting Akt in response to all-trans-retinoic acid. European Journal of cancer. 2012. Imran M, Park TJ, Lim IK.  
  • Loss of p21(Sdi1) expression in senescent cells after DNA damage accompanied with increase of miR-93 expression and reduced p53 interaction with p21(Sdi1) gene promoter. Biochem Biophys Res Commun. 2011 407, 406-411. Choi OR, Lim IK.
  • Reduction of exportin 6 activity leads to actin accumulation via failure of RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells. Exp Cell Res. 2011 317(7), 941-954. Su Hyun Park, Park, Tae Jun, Lim, In Kyoung,
  • Skp2 enhances polyubiquitination and degradation of TIS21/BTG2/PC3, tumor suppressor protein, at the downstream of FoxM1. Exp Cell Res. 2009 Nov 1;315(18):3152-62. Park TJ, Kim JY, Park SH, Kim HS, Lim IK.
  • Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate Sp1 on serine 59 and regulate cellular senescence via transcription of p21Sdi1/Cip1/Waf1. J Biol Chem. 2009 Jun 5;284(23):15475-86. Kim HS, Lim IK.
  • B cell translocation gene 2 (BTG2) enhances susceptibility of HeLa cells to doxorubicin-induced oxidative damage. J Biol Chem. 2008 Nov 28;283(48):33110-8. Lim YB, Park TJ, Lim IK.
  • Enhanced glycogenesis is involved in cellular senescence via GSK3/GS modulation. Aging Cell. 2008 Dec;7(6):894-907. Seo YH, Jung HJ, Shin HT, Kim YM, Yim H, Chung HY, Lim IK, Yoon G.
  • TIS21/(BTG2) negatively regulates estradiol-stimulated expansion of hematopoietic stem cells by derepressing Akt phosphorylation and inhibiting mTOR signal transduction. Stem Cells. 2008 Sep;26(9):2339-48. Kim BC, Ryu MS, Oh SP, Lim IK.
  • TIS21 negatively regulates hepatocarcinogenesis by disruption of cyclin B1-Forkhead box M1 regulation loop. Hepatology. 2008 May;47(5):1533-43. Park TJ, Kim JY, Oh SP, Kang SY, Kim BW, Wang HJ, Song KY, Kim HC, Lim IK.
  • TIS21 (/BTG2/PC3) as a link between ageing and cancer: cell cycle regulator and endogenous cell death molecule. J Cancer Res Clin Oncol. 2006 Jul;132(7):417-26. Review. Lim IK.
  • Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1 binding in cytoplasm and cell death. J Biol Chem.2005 Jun 3;280(22):21256-63. Hong JW, Ryu MS, Lim IK.
  • TIS21/BTG2/PC3 is expressed through PKC-delta pathway and inhibits binding of cyclin B1-Cdc2 and its activity, independent of p53 expression. Exp Cell Res.2004 Sep 10;299(1):159-70. Ryu MS, Lee MS, Hong JW, Hahn TR, Moon E, Lim IK.
  • Nuclear accumulation of globular actin as a cellular senescence marker. Cancer Res. 2004 Jan 15;64(2):572-80. Kwak IH, Kim HS, Choi OR, Ryu MS, Lim IK.
  • Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence. J Biol Chem. 2003 Sep 26;278(39):37497-510. Kim HS, Song MC, Kwak IH, Park TJ, Lim IK.
  • Spectrum of molecular changes during hepatocarcinogenesis induced by DEN and other chemicals in Fisher 344 male rats [Mechanisms of Ageing and Development 123 (2002) 1665-1680]. Mech Ageing Dev.2003 May;124(5):697-708. Lim IK.
Review article;
  • Lim, IK. (1986) Chemical carcinogenesis. Korean Biochem. J. 6:3-33.
  • Lim IK. (2002)Overview of cancer biology and therapeutics. Exp Mol Med.34 (Supplement):3-9.
  • Lim IK. (2002)Oncogene and cell transformation. Exp Mol Med. 34(Supplement):13-29
  • Lim IK. Spectrum of molecular changes during hepatocarcinogenesis induced by DEN and other chemicals in Fischer 344 male rats. Mech Ageing Dev. 2003 124:697-708.
  • Lim IK. (2006) TIS21/BTG2/PC3 as a link between ageing and cancer: Cell cycle regulator and endogenous cell death molecule. J Cancer Res Clin Oncology, 2006 Feb 3;1-10
Book Chapter:
  • In Kyoung Lim, Park, Tae Jun, In Hae Kwak and Woon Ki Paik: Molecular mechanism of tumor promotion by decreased testosterone during N-diethylnitrosamine/nodularin induced hepatocarcinogenesis in Fisher 344 male rat.  Liver carcinogenesis, Hepatitis B and C and Hepatocellular Cancer; 2nd International Congress on Gastroenterological Carcinogenesis, p75-82.1999. Editted by HG Beger and KH Link, Monduzzi Editore International Proceedings Division, Universitat Ulm (ISBN 88-323-0325-6).
  • Hyang-Woo Lee , Jeung Whan Han, Sung-Youl Hong, Sangduk Kim, Woon Ki Paik, In Kyoung Lim: Nitric oxide synthase in bacteria and mammalian tissues. FC5-1. The 5th International Symposium on Guanido Compounds in Biology and Medicine. Tokyo: Blackwell Science Japan, 1999. Chapter 35, Guanine compounds: 5 edited by A. Mori, Ishida and J.F. Clark. Blackwell Science Asia Pty Ltd. pp305-313.
  • In Kyoung Lim, Kwang Won Hong, In Hae Kwak, Gyesoon Yoon and Sang Chul Park: Translocational Inefficiency of Intracellular Proteins in Senescence of Human Diploid Fibroblasts. Ann New York Acad Sci, vol. 928: 176-181, 2001.
Laboratory of Cellular Senescence and Carcinogenesis (LCSC)

members of the picture

  • 최정아Jung-A Choi (최정아), Ph.D.
    Dr. Choi is a research fellow. She received her Ph.D from Korea University, Seoul, Korea in 2009. Her main interest is “Regulation of invasion/metastasis by tumor suppressor, TIS21/BTG gene”.
    size75@hanmail.net. Tel: 82-31-219-4499

  • 유민숙Min Sook Ryu (유민숙), Ph.D.
    Min Sook Ryu is a Lab manager in the LCSC. She received her Ph.D in the Biological Sciences from Ajou University School of Medicine, Suwon, Korea in 2005. Her current work is “Epigenetic regulation of TIS21/BTG2/Pc3 gene expression in ES and cancer cells”.
    msryubio@empal.com. Tel: 82-31-219-4496

  • 최용원Yong Won Choi (최용원), M.D.
    Dr. Choi is a MD-Ph.D stduent. He had graduated from Ajou University School of Medicine, Korea, in 2004 and had received a specialist board after training in the Department of Internal Medicine, Ajou University Hospital in 2009. His current work is “Regulation of necrotic cell death by tumor suppressor gene, TIS21/BTG2, in the cardiomyoblast”.
    dreamliebe@hanmail.net Tel: 82-31-219-5056

  • ImranMuhammad Imran (임란). MS
    Muhammad Imran is a Ph.D. candidate. He received his MS in Chemistry from University of Peshawar, Peshawar, Pakistan in 2006. His current work is “Differentiation of hematopoietic precursor cells by tumor suppressor, TIS21/BTG gene”.
    imrancl@hotmail.com Tel: 82-31-219-4496

  • 이윤영Yun Yeong Lee (이윤영). MS.
    Yun Yeong Lee is a Ph.D. candidate. He received his MS in Microbiology from Dong-eui University, Busan, Korea in 2009. His current work is “Understanding cellular senescence and senescence-related diseases”.
    seven260@naver.com. Tel: 82-31-219-4496

  • Sundaramoorthy SanthoshkumarSundaramoorthy Santhoshkumar (산토시).
    Sundaramoorthy Santhoshkumar is a Ph.D. student. He received his M.Sc in Biochemistry from University of Madras, Chennai, India in 2008. His current project is a function of TIS21/BTG2 on antioxidant regulation in HeLa cells. biosanthosh@gmail.com. Tel: 82-31-219-4496

  • Preethi DevanandPreethi Devanand (프리티).
    Preethi Devanand is a Ph.D. student. She received her M.Sc in Biochemistry from Adhiparasakthi College of Arts and Sciences, Thiruvalluvar University, Vellore, India in 2009. Her current research is “Analyzing epigenetic changes of tumor suppressor gene, TIS21/BTG2, by demethylating agents”.
    biopreethi@gmail.com Tel: 82-31-219-4496

  • 김빛나Bit Na Kim (김빛나).
    Bit-Na Kim is a Master student. She received her BS in Biology from Honam University, Kwangju, Korea in 2011. Her current work is related to function of actinin-remodeling network in carcinogenesis and cellular senescence. bnk801@ajou.ac.kr Tel: 82-31-219-4496

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