2014 MRC
[ ]
심포지엄 구연 발표
[O ]
기초의과학 학문후속세대 발표
( 연제와 관련있는 분야에 모두 표시해 주십시오 )
[ ] Aging and age-related diseases
[ ] Alternative medicine
[ ] Anatomical methodology
[ ] Anticancer strategies
[ ] Bioengineering and technology
[ ] Biology of development
[ ] Biomarkers for personalized medicine
[ ] Biomedical informatics
[ ] Cancer biology (oncological sciences)
[ O ] Cellular injuries, death, apoptosis, autophagy
[ ] Clinical pharmacology
[ ] Craniofacial diseases
[ ] Developmental Biology and Cell Differentiation
[ O ] DNA Replication, DNA Damage and Cell Cycle
[ ] Drug: mechanism of action & toxicity
[ ] Endocrinology and metabolism
[ ] Enzyme: mechanism of action and regulation
[ O ] Gene expression
[ ] Gene-, Cell-, & Immunotherapy
[ ] Genetics and Epigenetics
[ ] Gross anatomy
[ ] Herb medicine and phytochemicals
[ ] Histology of organs
[ ] Immunology
[ ] Inflammation and tissue injury
[ ] Infectious diseases: bacteriology, virology and mycology
[ ] Ion, ion channel & excitability
[ ] Membrane transport & secretion
[ ] Metabolic diseases
[ ] Molecular and Cellular Aspects of Behaviour
[ ] Neuroscience and Neurobiology
[ ] Novel Targets for Drug Development and Screening Candidates
[ ] Omics and Systems Biology
[ ] Orofacial Diseases
[ ] Protein Biochemistry: Structure, Function, and Modification
[ ] Parasitology and parasitic diseases
[ ] Pharmacogenetics
[ ] Preventive medicine
[ ] RNA Biology and Application
[ ] Signal transduction
[ ] Stem cells and regeneration
[ ] Therapeutic approaches of Korean Medicine
[ ] Vascular Biology and Medicine
[ ] 기타 ( )

An unresolved issue in genotoxic stress response is identification of induced regulatory proteins and how these activate tumor suppressor p53 to determine appropriate cell responses. Transcription factor KAISO was previously described to repress transcription following binding to methylated DNA. In this study, we show that KAISO is induced by DNA damage in p53-expressing cells and then interacts with the p53– p300 complex to increase acetylation of p53 K320 and K382 residues, although decreasing K381 acetylation. Moreover, the p53 with this particular acetylation pattern shows increased DNA binding and potently induces cell cycle arrest and apoptosis by activating transcription of CDKN1A (cyclin-dependent kinase inhibitor 1) and various apoptotic genes. Analogously, in Kaiso KO mouse embryonic fibroblast cells, p53-to-promoter binding and up-regulation of p21 and apoptosis gene expression is significantly compromised. KAISOmay therefore be a critical regulator of p53-mediated cell cycle arrest and apoptosis in response to various genotoxic stresses in mammalian cells
1. Daniel JM, Reynolds AB (1999) The catenin p120(ctn) interacts with Kaiso, a novel BTB/
POZ domain zinc finger transcription factor. Mol Cell Biol 19(5):3614–3623.
2. van Roy FM, McCrea PD (2005) A role for Kaiso-p120ctn complexes in cancer? Nat Rev
Cancer 5(12):956–964.
3. Wade PA (2001) Methyl CpG-binding proteins and transcriptional repression. Bio-
Essays 23(12):1131–1137.
4. Prokhortchouk A, et al. (2001) The p120 catenin partner Kaiso is a DNA
Methylationdependent transcriptional repressor. Genes Dev 15(13):1613–1618.
5. Daniel JM, Spring CM, Crawford HC, Reynolds AB, Baig A (2002) The p120(ctn)- binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. Nucleic Acids Res
30(13):2911–2919.
6. Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (2003) N-CoR mediates DNA methylationdependent repression through amethyl CpG binding protein Kaiso. Mol Cell
12(3):723–734.
7. Lopes EC, et al. (2008) Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. Cancer Res 68(18):7258–7263.
8. Soubry A, et al. (2010) The transcriptional repressor Kaiso localizes at the mitotic

spindle and is a constituent of the pericentriolar material. PLoS ONE 5(2):e9203.
9. Prokhortchouk A, et al. (2006) Kaiso-deficient mice show resistance to intestinal cancer.
Mol Cell Biol 26(1):199–208.
10. Vousden KH, Lane DP (2007) p53 in health and disease. Nat RevMol Cell Biol 8(4):275–283.
11. Polager S, Ginsberg D (2009) p53 and E2f: Partners in life and death. Nat Rev Cancer 9(10):738–748.
12. Knights CD, et al. (2006) Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate. J Cell Biol 173(4):533–544.
13. Appella E, Anderson CW(2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 268(10):2764–2772.
14. Avantaggiati ML, et al. (1997) Recruitment of p300/CBP in p53-dependent signal pathways.
Cell 89(7):1175–1184.
15. Strasser A (2005) The role of BH3-only proteins in the immune system. Nat Rev Immunol
5(3):189–200.
16. Nakano K, Vousden KH (2001) PUMA, a novel proapoptotic gene, is induced by p53.
Mol Cell 7(3):683–694.
17. Yu J, Zhang L (2008) PUMA, a potent killer with or without p53. Oncogene 27(Suppl 1):
S71–S83.
18. Danial NN, Korsmeyer SJ (2004) Cell death: Critical control points. Cell 116(2):205–219.
19. MacLachlan TK, El-Deiry WS (2002) Apoptotic threshold is lowered by p53 transactivation of caspase-6. Proc Natl Acad Sci USA 99(14):9492–9497.
20. Fridman JS, Lowe SW (2003) Control of apoptosis by p53. Oncogene 22(56):9030–9040.
21. Kelly KF, Daniel JM (2006) POZ for effect—POZ-ZF transcription factors in cancer and development. Trends Cell Biol 16(11):578–587.
22. Sansom OJ, Maddison K, Clarke AR (2007) Mechanisms of disease: Methyl-binding domain proteins as potential therapeutic targets in cancer. Nat Clin Pract Oncol 4(5):305–315.
23. Kruse J-P, Gu W (2009) Modes of p53 regulation. Cell 137(4):609–622.
24. Barlev NA, et al. (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 8(6):1243–1254.
25. Burns TF, Bernhard EJ, El-Deiry WS (2001) Tissue specific expression of p53 target genes suggests a key role for KILLER/DR5 in p53-dependent apoptosis in vivo. Oncogene
20(34):4601–4612.
26. Fuchs EJ, McKenna KA, Bedi A (1997) p53-dependent DNA damage-induced apoptosis requires Fas/APO-1-independent activation of CPP32beta. Cancer Res 57(13):2550–2554.
27. Levine AJ, Oren M (2009) The first 30 years of p53: Growing ever more complex. Nat
Rev Cancer 9(10):749–758.
28. Bode AM, Dong Z (2004) Post-translational modification of p53 in tumorigenesis. Nat

Rev Cancer 4(10):793–805.
29. Dai C, Gu W (2010) p53 post-translational modification: Deregulated in tumorigenesis.
Trends Mol Med 16(11):528–536.
30. Lill NL, Grossman SR, Ginsberg D, DeCaprio J, Livingston DM (1997) Binding and modulation of p53 by p300/CBP coactivators. Nature 387(6635):823–827.
31. Gu W, Roeder RG (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90(4):595–606.
32. Puca R, et al. (2009) HIPK2 modulates p53 activity towards pro-apoptotic transcription.
Mol Cancer 8(85):85.
33. Riley T, Sontag E, Chen P, Levine A (2008) Transcriptional control of human p53- regulated genes. Nat Rev Mol Cell Biol 9(5):402–412.
34. Kelly KF, Spring CM, Otchere AA, Daniel JM (2004) NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression. J Cell
Sci 117(Pt 13):2675–2686.
35. Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc 1(6):2856–2860.
36. Olsen JV, et al. (2009) A dual pressure linear ion trap Orbitrap instrument with very high sequencing speed. Mol Cell Proteomics 8(12):2759–2769.
Keywords : KAISO, p53, cell cycle arrest, apoptosis, p300

2014 MRC
박사 후 연구원
Institution Attended
Dept. Biochemistry & Molecular Biology,
Yonsei University School of Medicine
Dept. Biochemistry & Molecular Biology,
Yonsei University School of Medicine
Dept. Bioscience,
Yonsei University School
Degree & Year
Ph.D. 2014. 02
M.S. 2010. 02
B.S. 2006. 02
(less than 5 experiences)
Institution
Dept. Biochemistry & Molecular Biology,
Yonsei University School of Medicine
Position
Teaching assistant
Pi cture
Mentor
Man-Wook, Hur
Man-Wook, Hur
Myung-Won Kim
From – To
2014
(less than 5 papers)
1. Koh DI, Han D, Ryu H, Choi WI, Jeon BN, Kim MK, Kim Y, Kim JY, Parry L, Clarke AR, Reynolds
AB, Hur MW. KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes. Proc Natl Acad Sci U S A. 2014 Oct 6. Epub ahead of print.

2. Jeon BN, Kim MK, Yoon JH, Kim MY, An H, Noh HJ, Choi WI, Koh DI, Hur MW. Two ZNF509
(ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress. Nucleic Acids Res. 2014 Sep 22. Epub ahead of print.
3. Choi WI, Yoon JH, Kim MY, Koh DI, Licht JD, Kim K, Hur MW. Promyelocytic leukemia zinc fingerretinoic acid receptor α (PLZF-RARα), an oncogenic transcriptional repressor of cyclin-dependent kinase inhibitor 1A (p21WAF/CDKN1A) and tumor protein p53 (TP53) genes. J Biol Chem. 2014 Jul
4;289(27):18641-56.
4. Choi WI, Kim MY, Jeon BN, Koh DI, Yun CO, Li Y, Lee CE, Oh J, Kim K, Hur MW. Role of promyelocytic leukemia zinc finger (PLZF) in cell proliferation and cyclin-dependent kinase inhibitor
1A (p21WAF/CDKN1A) gene repression. J Biol Chem. 2014 Jul 4;289(27):18625-40.
5. Yoon JH, Choi WI, Jeon BN, Koh DI, Kim MK, Kim MH, Kim J, Hur SS, Kim KS, Hur MW. Human
Kruppel-related 3 (HKR3) is a novel transcription activator of alternate reading frame (ARF) gene. J
Biol Chem. 2014 Feb 14;289(7):4018-31