Jiandong Chen, PhD

Our laboratory mainly focuses on studying the p53 pathway in tumor cells. Recent work involve the p53 regulator MDMX. We are investigating the regulation of MDMX by ubiquitination and phosphorylation, the roles of MDMX in regulating p53 response to DNA damage and ribosomal stress, and the role of MDMX in tumor formation. We are also trying to develop inhibitors against MDM2 and MDMX as therapeutic agents. A second area of research addresses the role of SirT1 in stress response in tumor cells, regulation of SirT1 expression by E2F1, and the role of SirT1 phosphorylation.

• Song T, Yang L, Kabra N, Chen L, Koomen J, Haura EB, Chen J. The NAD+ synthesis enzyme NMNAT1 regulates rRNA transcription. J Biol Chem. 2013 Jun. Pubmedid: 23737528.
• Gray JE, Altiok S, Alexandrow MG, Walsh FW, Chen J, Schell MJ, Tai DF, Bepler G. Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers. Cancer. 2013 Mar;119(5):1023-1032. Pubmedid: 23065656. Pmcid: PMC3578040.
• Zheng H, Chen L, Pledger WJ, Fang J, Chen J. p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene. 2013 Feb. Pubmedid: 23376847.
• Wu S, Chen L, Becker A, Schonbrunn E, Chen J. Casein kinase 1? regulates an MDMX intramolecular interaction to stimulate p53 binding. Mol Cell Biol. 2013 Jan;32(23):4821-4832. Pubmedid: 23028042. Pmcid: PMC3497597.
• Hodul PJ, Dong Y, Husain K, Pimiento JM, Chen J, Zhang A, Francois R, Pledger WJ, Coppola D, Sebti SM, Chen DT, Malafa MP. Vitamin E ?-Tocotrienol Induces p27(Kip1)-Dependent Cell-Cycle Arrest in Pancreatic Cancer Cells via an E2F-1-Dependent Mechanism. PLoS One. 2013;8(2):e52526. Pubmedid: 23393547.
• Tang J, Agrawal T, Cheng Q, Qu L, Brewer MD, Chen J, Yang X. Phosphorylation of Daxx by ATM Contributes to DNA Damage-Induced p53 Activation. PLoS One. 2013;8(2):e55813. Pubmedid: 23405218. Pmcid: PMC3566025.
• Peng L, Ling H, Yuan Z, Fang B, Bloom G, Fukasawa K, Koomen J, Chen J, Lane WS, Seto E. SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60. Mol Cell Biol. 2012 Jul;32(14):2823-2836. Pubmedid: 22586264. Pmcid: PMC3416197.
• Chen J. The Roles of MDM2 and MDMX Phosphorylation in Stress Signaling to p53. Genes Cancer. 2012 Mar;3(3-4):274-282. Pubmedid: 23150760. Pmcid: PMC3494364.
• Peng L, Yuan Z, Ling H, Fukasawa K, Robertson K, Olashaw N, Koomen J, Chen J, Lane WS, Seto E. SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities. Mol Cell Biol. 2011 Dec;31(23):4720-4734. Pubmedid: 21947282. Pmcid: PMC3232929.
• Cross B, Chen L, Cheng Q, Li B, Yuan ZM, Chen J. Inhibition of p53 DNA binding function by the MDM2 protein acidic domain. J Biol Chem. 2011 Jul;286(18):16018-16029. Pubmedid: 21454483. Pmcid: PMC3091211.
• Madden MM, Muppidi A, Li Z, Li X, Chen J, Lin Q. Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition. Bioorg Med Chem Lett. 2011 Jun;21(5):1472-1475. Pubmedid: 21277201. Pmcid: PMC3057119.
• Cheng Q, Chen J. The phenotype of MDM2 auto-degradation after DNA damage is due to epitope masking by phosphorylation. Cell Cycle. 2011 Apr;10(7):1162-1166. Pubmedid: 21386656. Pmcid: PMC3100889.
• Hu Y, Li X, Sebti SM, Chen J, Cai J. Design and synthesis of AApeptides: A new class of peptide mimics. Bioorg Med Chem Lett. 2011 Mar;21(5):1469-1471. Pubmedid: 21292484.
• Li B, Cheng Q, Li Z, Chen J. p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors. Cell Cycle. 2011 Mar;9(7):1411-1420. Pubmedid: 20372076. Pmcid: PMC3008305.
• Chen L, Li Z, Zwolinska AK, Smith MA, Cross B, Koomen J, Yuan ZM, Jenuwein T, Marine JC, Wright KL, Chen J. MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. EMBO J. 2010 Aug;29(15):2538-2552. Pubmedid: 20588255. Pmcid: PMC2928696.
• Yuan Z, Villagra A, Peng L, Coppola D, Glozak M, Sotomayor EM, Chen J, Lane WS, Seto E. The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions. Mol Cell Biol. 2010 Jun;30(12):3004-3015. Pubmedid: 20368352. Pmcid: PMC2876676.
• Kim D, Sun M, He L, Zhou QH, Chen J, Sun XM, Bepler G, Sebti SM, Cheng JQ. A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation. J Biol Chem. 2010 Apr;285(11):8383-8394. Pubmedid: 20068047. Pmcid: PMC2832988.
• Cheng Q, Chen J. Mechanism of p53 stabilization by ATM after DNA damage. Cell Cycle. 2010 Feb;9(3):472-478. Pubmedid: 20081365. Pmcid: PMC2977994.
• Zhang Y, Dong H, Li Z, Xiang S, Zhu Y, Zhang M, Liu J, Bai W, Nicosia SV, Chen J. Bing De Ling, a Chinese herbal formula, inhibits cancer cells growth via p53. Front Biosci (Elite Ed). 2010 Jan;2:221-230. Pubmedid: 20036872.
• Phan J, Li Z, Kasprzak A, Li B, Sebti S, Guida W, Schönbrunn E, Chen J. Structure-based design of high affinity peptides inhibiting the interaction of p53 with MDM2 and MDMX. J Biol Chem. 2010 Jan;285(3):2174-2183. Pubmedid: 19910468. Pmcid: PMC2804373.
• Cheng Q, Chen L, Li Z, Lane WS, Chen J. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J. 2010 Jan;28(24):3857-3867. Pubmedid: 19816404. Pmcid: PMC2797053.
• Lawrence HR, Li Z, Yip ML, Sung SS, Lawrence NJ, McLaughlin ML, McManus GJ, Zaworotko MJ, Sebti SM, Chen J, Guida WC. Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. Bioorg Med Chem Lett. 2009 Oct;19(14):3756-3759. Pubmedid: 19457663. Pmcid: PMC2754843.
• Fu W, Ma Q, Chen L, Li P, Zhang M, Ramamoorthy S, Nawaz Z, Shimojima T, Wang H, Yang Y, Shen Z, Zhang Y, Zhang X, Nicosia SV, Zhang Y, Pledger JW, Chen J, Bai W. MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation. J Biol Chem. 2009 Jul;284(21):13987-14000. Pubmedid: 19321440. Pmcid: PMC2682847.
• Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, Yeatman T, Coppola D, Chen J. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 2009 Jul;284(27):18210-18217. Pubmedid: 19433578. Pmcid: PMC2709385.
• Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem. 2009 Jun;284(17):11171-11183. Pubmedid: 19265193. Pmcid: PMC2670122.
• Shaginian A, Whitby LR, Hong S, Hwang I, Farooqi B, Searcey M, Chen J, Vogt PK, Boger DL. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions. J Am Chem Soc. 2009 Apr;131(15):5564-5572. Pubmedid: 19334711. Pmcid: PMC2765553.
• Li Z, Chen L, Kabra N, Wang C, Fang J, Chen J. Inhibition of SUV39H1 methyltransferase activity by DBC1. J Biol Chem. 2009 Apr;284(16):10361-10366. Pubmedid: 19218236. Pmcid: PMC2667723.
• Gilkes DM, Pan Y, Coppola D, Yeatman T, Reuther GW, Chen J. Regulation of MDMX expression by mitogenic signaling. Mol Cell Biol. 2008 Mar;28(6):1999-2010. Pubmedid: 18172009.
• Wang C, Rauscher FJ 3rd, Cress W, Chen J. Regulation of E2F1 function by the nuclear co-repressor KAP-1. J Biol Chem. 2007 Oct;282(41):29902-9. Pubmedid: 17704056.
• Hu B, Gilkes D, Chen J. Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding toMDM2 and MDMX. Cancer Res. 2007 Sep;67(18):8810-8817. Pubmedid: 17875722.
• Gilkes D, Chen J. Distinct roles of MDMX in the regulation of p53 response to ribosomal stress. Cell Cycle. 2007 Jan;6(2):151-5. Epub 20. Pubmedid: 17327702.
• Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem. 2006 Nov;281(44):33030-33035. Pubmedid: 16905541.
• Gilkes DM, Chen L, Chen J. MDMX regulation of p53 response to ribosomal stress. EMBO J. 2006 Nov;25(23):5614-5625. Pubmedid: 17110929.
• Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y, Nemoto S, Finkel T, Gu W, Cress WD, Chen J. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006 Sep;8(9):1025-1031. Pubmedid: 16892051.
• Lebron C, Chen L, Gilkes DM, Chen J. Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. Embo J. 2006 Apr;25(6):1196-1206. Pubmedid: 16511560. Pmcid: PMC1422166.
• Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. Embo J. 2006 Mar;24(19):3411-3422. Pubmedid: 16163388. Pmcid: PMC1276172.
• Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJ, Chen J. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. Embo J. 2005 Nov;24(18):3279-3290. Pubmedid: 16107876. Pmcid: PMC1224681.
• Chen L, Li C, Pan Y, Chen J. Regulation of p53-MDMX interaction by casein kinase 1 alpha. Mol Cell Biol. 2005 Aug;25(15):6509-6520. Pubmedid: 16024788. Pmcid: PMC1190343.
• Pan Y, Chen J. Modification of MDMX by sumoylation. Biochem Biophys Res Commun. 2005 Jul;332(3):702-709. Pubmedid: 15907800.
• Chen L, Yin H, Farooqi B, Sebti S, Hamilton AD, Chen J. p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53. Mol Cancer Ther. 2005 Jun;4(6):1019-1025. Pubmedid: 15956260.
• Wang C, Hou X, Mohapatra S, Ma Y, Cress WD, Pledger WJ, Chen J. Activation of p27Kip1 Expression by E2F1. A negative feedback mechanism. J Biol Chem. 2005 Apr;280(13):12339-12343. Pubmedid: 15713665.
• Liu Q, Kaneko S, Yang L, Feldman RI, Nicosia SV, Chen J, Cheng JQ. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem. 2004 Dec;279(50):52175-52182. Pubmedid: 15469940.
• Wang J, Gamsby J, Highfill S, Mora L, Bloom G, Yeatman T, Pan T, Ramne A, Chodosh L, Cress W, Chen J, Kerr W. Deregulated expression of LRBA facilitates cancer cell growth. Oncogene. 2004;23(23):4089-4097. Pubmedid: 15064745.
• Pan Y, Chen J. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol. 2003 Aug;23(15):5113-5121. Pubmedid: 12860999. Pmcid: PMC165735.
• Peng Y, Li C, Chen L, Sebti S, Chen J. Rescue of mutant p53 transcription function by ellipticine. Oncogene. 2003 Jul;22(29):4478-4487. Pubmedid: 12881704.
• Chen L, Chen J. MDM2-ARF complex regulates p53 sumoylation. Oncogene. 2003;22(34):5348-5357. Pubmedid: 12917636.
• Li C, Chen L, Chen J. DNA damage induces MDMX nuclear translocation by p53-dependent and -independent mechanisms. Mol Cell Biol. 2002 Nov;22(21):7562-7571. Pubmedid: 12370303. Pmcid: PMC135668.
• Lu W, Lin J, Chen J. Expression of p14ARF overcomes tumor resistance to p53. Cancer Res. 2002 Mar;62(5):1305-1310. Pubmedid: 11888896.
• Wang C, Chen J. Phosphorylation and hsp90 binding mediate heat shock stabilization of p53. J Biol Chem. 2002;278:2066-2071.
• Li K, Wang L, Cheng J, Lu Y, Zhang L, Mou J, Hong Y, Liu Y, Duan H, Wang G, Li L, Chen J. [Mutual interaction between hepatitis C virus core protein and translin, arecombination hotspot binding protein] Chinese. Zhonghua Yi Xua Za Zhi. 2002;82:673-677. Pubmedid: 12133464.
• Zhong Y, Cheng J, Wang G, Tian X, Chen X, Liu Y, Li L, Zhang L, Chen J. [Epitope mapping of hepatitis C virus non-structure protein 5 from a 7 peptidephage library by using immobilized specific monoclonal antibody]Zhonghua Gan Zang Bing Za Zhi. 2002;10:266-8. Ch. Pubmedid: 12223135.
• Li K, Wang L, Cheng J, Lu Y, Zhang L, Mou J, Hong Y, Liu Y, Duan H, WangG, Li L, Chen J. [Mutual interaction between hepatitis C virus core protein and translin, arecombination hotspot binding protein]Zhonghua Yi Xue Za Zhi. 2002;82:673-7. Ch. Pubmedid: 12133464.
• Lu W, Chen L, Peng Y, Chen J. Activation of p53 by roscovitine-mediated suppression of MDM2 expression. Oncogene. 2001;20(25):3206-3216. Pubmedid: 11423970.
• Peng Y, Chen L, Li C, Lu W, Chen J. Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J Biol Chem. 2001;276(44):40583-40590. Pubmedid: 11507088.
• Peng Y, Chen L, Li C, Lu W, Agrawal S, Chen J. Stabilization of the MDM2 ocoprotein by mutant p53. J Biol Chem. 2001;276(9):6874-6878. Pubmedid: 11152666.
• Pochampally R, Li C, Lu W, Chen L, Luftig R, Lin J, Chen J. Temperature-sensitive mutants of p53 homologs. Biochem Biophys Res Commun. 2000;279(3):1001-1010. Pubmedid: 11162465.
• Pochampally R, Fodera B, Chen L, Shao W, Levine E, Chen J. A 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells. Oncogene. 1999;17:2629-2636. Pubmedid: noPMID.
• Pochampally R, Fodera B, Chen L, Lu W, Chen J. Activation of an MDM2-specific caspase by p53 in the absence of apoptosis. J Biol Chem. 1999;274:15271-15277. Pubmedid: 10329737.
• Chen L, Lu W, Agrawal S, Zhou W, Zhang R, Chen J. Ubiquitous induction of wild type p53 in tumor cells by antisense inhibition of MDM2 expression. Mol Med. 1999;5:19-32. Pubmedid: noPMID.
• Zeng X, Chen L, Jost C, Maya R, Kaelin W, Oren M, Chen J, Lu H. MDM2 supresses p73 function without promoting p73 degradation. Mol Cell Biol. 1999;19:3257-3266. Pubmedid: 10207051.
• Lu W, Pochampally R, Chen L, Traidej M, Wang Y, Chen J. Nuclear exclusion of p53 in a subset of tumors requires MDM2 function. Oncogene. 1999;19(2):232-240. Pubmedid: 10645001.
• Chen L, Agrawal S, Zhou W, Zhang R, Chen J. Synergistic activation of p53 by inhibitation of mdm2 expression and DNA damage. Proc Natl Acad Sci U S A. 1998;95:195-200. Pubmedid: 9419352.
• Chen L, Marechal V, Moreau J, Levine A, Chen J. Proteolytic cleavage of the mdm2 oncoprotein during apoptosis. J Biol Chem. 1997;272:22966-22973. Pubmedid: 9278461.
• Chen J, Wu X, Lin J, Levine A. Mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol Cell Biol. 1996;16:2445-2452. Pubmedid: 8628312.
• Chen J, Lin J, Levine A. Regulation of transcription functions of the p53 tumor supressor by the mdm-2 oncogene. Mol Med. 1995;1:142-152. Pubmedid: 8529093.
• Horikoshi N, Usheva A, Chen J, Levine A, Weinmann R, Shenk T. Two domains on p53 interat with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression. Mol Cell Biol. 1995;15:227-234. Pubmedid: 7799929.
• Xiao Z, Chen J, Levine A, Modjtahedi N, Xing J, Sellers W, Livingston D. Interation between the retinoblastoma protein and the oncoprotein. Nature. 1995;375:694-698. Pubmedid: 7791904.