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Ahn, Jin Hyun, Associate Professor

Molecular Virology Laboratory
Department of Molecular Cell Biology
Sungkyunkwan University School of Medicine
300 Chunchundong, Jangangu
Suwon, Gyonggido 440-746
Korea
Tel: +82-31-299-6222
Fax: +82-31-299-6239
e-mail: jahn@skku.edu

Education and Experiences:

Mar. 2001 - present :

Assistant/Associate Professor, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine

Mar. 2000 - Feb. 2001:

Research Associate, Department of Oncology, Johns Hopkins University School of Medicine, U.S.A.

Sep. 1994 - Dec. 1999:

Postdoctoral Fellow in Molecular Virology Laboratory, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, U.S.A.

Mar. 1988 - Feb. 1994:

Ph.D. in Molecular Biology and Genetics, Department of Microbiology, College of Natural Sciences, Seoul National University

Mar. 1986 - Feb. 1988:

M.S. in Microbiology, Department of Microbiology, College of Natural Sciences, Seoul National University

Mar. 1982 - Feb. 1986:

B.S. in Microbiology, Department of Microbiology, College of Natural Sciences, Seoul National University

Research Interest:

-       HCMV gene regulation, DNA replication, and virion maturation

-       Regulation of intrinsic and innate immune responses by herpesvirus

-       Interplay between virus and the Ub and Ubl-conjugating systems

Research of our laboratory focuses on the functions of viral immediate-early regulatory proteins, DNA replication proteins, and tegument proteins of human cytomegalovirus (HCMV), which belongs to a beta-herpesvirus subfamily and causes life-threatening diseases in congenital infection and infection of immunocompromised patients.  We also aim to understand the interaction between virus and host at the cellular level by studying the molecular mechanisms of host anti-viral defenses including intrinsic and innate immune responses and viral strategies against these host defenses.  We are also expanding our research on the interplay between the cellular ubiquitin (Ub) and Ub-like protein (Ubl)-conjugating systems and the viral regulatory proteins during infection.  We employ many state-of-the art technologies in molecular biology, biochemistry, and genetics to address the questions.  Our studies will help us understand how the viral proteins orchestrate viral gene expression and DNA replication during the progression of viral infection and modulate host functions to prepare the infected-host cells for the production of progeny virions.

 The detailed research projects we are currently working on are:

(i)            Isoform-specific functions of the PML and Sp100 proteins in viral gene regulation

(ii)          Covalent and non-covalent interactions of IE2 with SUMO

(iii)        Regulation of cellular ISGylation during herpesvirus infection

(iv)        Assembly of HCMV DNA replication compartments

(v)          Role of the HCMV UL48 tegument protein in viral entry, nuclear egress, and maturation

(vi)        Function of the HCMV-encoded chemokine receptor UL144

(vii)      Role of the Z-DNA binding protein (ZBP1) during herpesvirus infection

(viii)    A cell-based screening system for small molecules inhibiting HCMV growth  

 

Recent Publications:

1.       Kim, Y.-E., and J.-H. Ahn. 2010. Role of the specific interaction of UL112-113 p84 with UL44 DNA polymerase processivity factor in promoting DNA replication of human cytomegalovirus. J. Virol. 84(17):8409-8421.

2.       Kim, E. T., Y.-E. Kim, Y. H. Huh, and J.-H. Ahn. 2010. Role of non-covalent SUMO binding by the human cytomegalovirus IE2 transactivator in lytic growth. J. Virol. 84(16):8111-8123.

3.       Kim, E.T.*, S. E. Oh*, Y.-O. Lee*, W. Gibson, and J.-H. Ahn.  2009. Cleavage specificity of the UL48 deubiquitinating protease activity of human cytomegalovirus and the growth of an active site mutant virus in cultured cells. J. Virol. 83(23):12046-12056. *These authors contributed equally in this paper.

4.       Yi, H. A., M. S. Kim, S. Y. Jang, Y. M. Lee, J.-H. Ahn, and C. H. Lee. 2009. Cellular signals involved in cyclooxygenase-2 expression induced by human cytomegalovirus. Virus Res. 146:89-96.

5.       Kim E. T., K. K. Kim, M. J. Matunis, and J.-H. Ahn. 2009. Enhanced SUMOylation of proteins containing a SUMO-interacting motif by SUMO-Ubc9 fusion. Biochem. Biophys. Res. Commun. 388:41-45.

6.       Oh, W, J. Ghim, E. W. Lee, M. R. Yang, E. T. Kim, J. H. Ahn, and J. Song. 2009. PML-IV functions as a negative regulator of telomerase by interacting with TERT. J. Cell Sci. 122:2613-2622.

7.       Min, H.-J., I.-R. Cho, R. Srisuttee, E.-H. Park, D. H. Cho, J.-H. Ahn, I.-S. Lee, R. N. Johnston, S. Oh, and Y.-H. Chung. 2009. Hexachlorophene suppresses b-catenin expression by up-regulation of Siah-1 in EBV-infected B lymphoma cells. Cancer Lett. 276(2):136-142.

8.       Koh, K., K. Lee, J.-H. Ahn, and S. Kim. 2009. Human cytomegalovirus infection downregulates the expression of glial fibrillary acidic protein in human glioblastoma cells, U373MG: identification of viral genes and protein domains involved. J. Gen. Virol. 90(4):954-962. 

9.       Ahn, J,-W., Y.-A. Lee, J.-H. Ahn, and C. Y. Choi. 2009. Covalent conjugation of Groucho with SUMO-1 modulates its corepressor activity. Biochem. Biophys. Res. Commun. 379(1):160-165.

10.   Huh Y. H., Y.-E. Kim, E. T. Kim, J. J. Park, M. J. Song, H. Zhu, G. S. Hayward, and J.-H. Ahn. 2008. Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO. J. Virol. 82(21):10444-10454.

11.   Moon J.-S., M.-Y. Lee, S. W. Park, W. K. Han, S.-W. Hong, J.-H. Ahn, and K.-S. Kim. 2008. Androgen-dependent activation of human cytomegalovirus major immediate-early promoter in prostate cancer cells. Prostate. 68(13):1450-1460.

12.   Park, J.-J.*, Y.-E. Kim*, H. T. Pham, E. T. Kim, Y.-H. Chung, and J.–H. Ahn. 2007. Functional interaction of the human cytomegalovirus IE2 protein with histone deacetylase 2 in infected human fibroblasts.  J. Gen. Virol. 88(12):3214-3223. *These authors contributed equally in this paper.

13.   Lee, S.-J., J.-R. Lee, H.-S. Hahn, Y.-H. Kim, J.-H. Ahn, C.-D. Bae, J.-M. Yang, and M.-J. Hahn. 2007. PIAS1 interacts with the KRAB zinc finger protein ZNF133, via zinc finger motifs and regulates its transcriptional activity. Exp. Mol. Med. 39(4):450-457

14.   Lee, H.-R., Y. H. Huh, Y.-E. Kim, K. Lee, S. Kim, and J.-H. Ahn. 2007. N-terminal determinants of human cytomegalovirus IE1 protein in nuclear targeting and disrupting PML-associated subnuclear structures. Biochem. Biophys. Res. Commun. 356(2):499-504.

15.   Pham, H. T., M.-Y. Park, K. K. Kim, Y. –G. Kim, and J.-H. Ahn. 2006. Intracellular localization of human ZBP1: differential regulation by the Z-DNA binding domain, Za, in splice variants. Biochem. Biophys. Res. Commun. 348:145-152.

16.   Kang, H*, E. T. Kim,* H.-R. Lee*, J.-J. Park, Y. Y. Go, C. Y. Choi, and J.-H. Ahn. 2006. Inhibition of SUMO-independent PML oligomerization by the human cytomegalovirus IE1 protein. J. Gen. Virol. 87:2181-2190. *These authors contributed equally in this paper.

17.   Park, M.-Y., Y.-E. Kim, M.-R. Seo, J.-R. Lee, C. H. Lee, and J.-H. Ahn. 2006. Interactions among four proteins encoded by human cytomegalovirus UL112-113 region regulate their intranuclear targeting and recruitment of UL44 to pre-replication foci. J. Virol. 80(6): 2718-2727.

18.   Ha, S.C., D. Van Quyen, H. Y. Hwang, D. B. Oh, B. A. Brown 2nd, S. M. Lee, H. J. Park, J. H. Ahn, K. K. Kim, Y. G. Kim. 2006. Biochemical characterization and preliminary X-ray crystallographic study of the domains of human ZBP1 bound to left-handed Z-DNA .2006. Biochimica et Biophysica Acta  (BBA) – Proteins & Proteomics 1764:320-323.

19.   Sung, K. S., Y. Y. Go, J.-H. Ahn, Y. H. Kim, Y. Kim, and C. Y. Choi. 2005. Differential interactions of the homeodomain-interacting protein kinase 2 (HIPK2) by phosphorylation-dependent sumoylation. FEBS Letters  579(1):3001-3008.

20.   Kim ,Y.-E., D.-Y. Kim, J.-M. Lee, S.-T. Kim, T.-H. Han, and J.-H. Ahn. 2005. Requirement of the coiled-coil domain of PML-RARa oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem. Biophys. Res. Commun. 330:746-754.

21.   Choi, S.-J., J.-H. Moon, Y.-W. Ahn, J.-H. Ahn, D.-U. Kim, and T.-H. Han. 2005. Tsc-22 enhances TGF-b signaling by associating with Smad4 and induces erythroid cell differentiation. Mol. Cell. Biochem. 271:23-28.

22.   Shin, J., B. Park, S. Cho, S. Lee, Y. Kim, S.-O. Lee, K. Cho. S. Lee, B.-S. Jin, J.-H. Ahn, E.-J. Choi, and K. Ahn. 2004. PML is a direct inhibitor of  SAPK2/p38 mitogen-activated protein kinase. J. Biol. Chem. 279(39):40994-41003.

23.   Lee, H.-R., and J.-H. Ahn. 2004. Sumoylation of the major immediate-early IE2 protein of human cytomegalovirus Towne strain is not required for virus growth in cultured human fibroblasts. J. Gen. Virol.  85:2149-2154.

24.   Lee, H.-R, D.-J. Kim, J.-M., Lee, C. Y. Choi, B.-Y. Ahn,  G. S. Hayward, and J.-H. Ahn. 2004. Ability of the human cytomegalovirus IE1 protein to modulate sumoylation of PML correlates with its functional activities in transcriptional regulation and infectivity in cultured fibroblast cells. J. Virol. 78(12): 6527-6542.

25.   Lee, J.-M, H.-J. Kang, H.-R. Lee, C. Y. Choi, W.-J. Jang, and J.-H. Ahn. 2003. PIAS1 enhances SUMO-1 modification and the transactivation activity of the major immediate-early IE2 protein of human cytomegalovirus. FEBS Letters 555(2):322-328.

26.   Chang, S.-K., B. Park, J. Shin, J.-H. Ahn, I.-H. Kim, and K. Ahn. 2002. Proto-oncogene PML enhances antigen presentation by MHC class I molecules in human lung cancer cells. Mol. Cells. 14:130-135.

27.   Xu, Y.*, J.-H. Ahn*, M. Cheng, C. M.. apRhys, C.-J. Chiou, J. Zong, M. J. Matunis, and G. S. Hayward. 2001.  Proteasome-independent disruption of PML oncogenic domains, but not covalent modification by SUMO-1, is required for the human cytomegalovirus immediate-early IE1 protein to inhibit PML-mediated transcriptional repression. J. Virol. 75:10683-10695. These authors contributed equally in this paper.

28.   Ahn, J.-H.*, Y. Xu*, W.-J. Jang, M. J. Matunis, and G. S. Hayward. 2001. Evaluation of Interactions of human cytomegalovirus immediate-early IE2 regulatory protein with small ubiquitin-like modifiers and their conjugation enzyme Ubc9. J. Virol. 75:3859-3872. These authors contributed equally in this paper.

29.   Wu, F., J.-H. Ahn, D. J. Alcendor, W. -J. Jang, J. Xiao, S. D. Hayward, and G. S. Hayward. 2001. Origin independent assembly of Kaposi’s sarcoma-associated herpesvirus (KSHV) DNA replication compartments in transient cotransfection assays and association with ORF-K8 protein and cellular PML (PODs). J. Virol. 75:1487-1506.

30.   Ahn, J.‑H., and G. S. Hayward. 2000. Disruption of PML‑associated nuclear bodies by IE1 correlates with  the efficient viral gene expression and replication in human cytomegalovirus infection. Virology 274:39-55.

31.   Lee, G.-C., C.-K. Lee, J.‑H. Ahn, and C.-H. Lee. 2000. Expression of human cytomegalovirus immediate early US3 gene in human fibroblast cells. J. Microbiol. 38:24-30.

32.   Ahn, J.‑H., W.‑J. Jang, and G. S. Hayward. 1999. The human cytomegalovirus IE2 and UL112‑113 proteins accumulate in the viral DNA replication compartments that initiate from the periphery of promyelocytic leukemia protein‑associated nuclear bodies (PODs or ND10). J. Virol. 73:10458-10471.

33.   Ahn, J.‑H., R. Sariski, I. Waheed, C.-J. Chiou, and G. S. Hayward. 1999. CMV replication: Formation of replication compartments and the role of accessory protein IE1, IE2, UL84 and PML. J. Clin. Virol. 12:85-92.

34.   Lee, C.‑H., G.‑C. Lee, Y.‑J. Chan, C.‑J. Chiou, J.‑H. Ahn, and G. S. Hayward. 1999. Factors affecting human cytomegalovirus gene expression in human monocyte cell lines.  Mol. Cells 9:37‑44.

35.   Waheed, I., C.‑J. Chiou, J.‑H. Ahn, and G. S. Hayward. 1998. Binding of the human cytomegalovirus 80‑kD immediate early protein (IE2) to minor groove A/T‑rich sequences bounded by CG dinucleotides is regulated by protein oligomerization and phosphorylation. Virology 252:235‑257.

36.   Lim, D.‑S., D. G. Kirsch, C. E. Canman, J.‑H. Ahn, Y. Ziv, L. S. Newman, R. B. Darnell, Y. Shiloh, and M. Kastan. 1998. Atm binds to beta‑Adaptin in cytoplasmic vesicles. Proc. Natl. Acad. Sci. USA  95:10146‑10151.

37.   Ahn, J.‑H., E. B. Brignole III, and G. S. Hayward. 1998. Disruption of PML subnuclear domains by the acidic IE1 protein of human cytomegalovirus is mediated through interaction with PML and may modulate a RING finger dependent cryptic transactivator function of PML. Mol. Cell. Biol. 18:4899‑4913.

38.   Ahn, J.‑H., C.‑J. Chiou, and G. S. Hayward. 1998. Evaluation and mapping of DNA binding and oligomerization domains of IE2 regulatory protein of human cytomegalovirus using yeast one and two hybrid interaction assays. Gene 210:25‑36.

39.   Ahn, J.‑H., and G. S. Hayward. 1997. The major immediate‑early proteins IE1 and IE2 of human cytomegalovirus colocalize with and disrupt PML‑associated nuclear bodies at very early times in infected permissive cells. J. Virol. 71:4599‑4613.