Jiandong Chen
Researcher

Jiandong Chen

Academic Rank: Senior Member

Overview

Our laboratory mainly focuses on studying the p53 pathway in tumor cells.

Discipline

    • Molecular Oncology
    • Cancer Biology and Evolution Program
    • Lung Cancer Center of Excellence

Education & Training

    • Princeton University, Postdoctoral Fellow - Molecular Biology
    • University of Pittsburgh, PhD - Molecular Biology
Research

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.

Publications

  • Borcherds W, Becker A, Chen L, Chen J, Chemes LB, Daughdrill GW. Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX. Biophys J. 2017 May;112(10):2038-2042. Pubmedid: 28487147. Pmcid: PMC5443996.
  • Chen J. The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression. Cold Spring Harb Perspect Med. 2016 Mar;6(3):a026104. Pubmedid: 26931810.
  • Yang L, Song T, Chen L, Soliman H, Chen J. Nucleolar repression facilitates initiation and maintenance of senescence. Cell Cycle. 2015 Nov;14(22):3613-3623. Pubmedid: 26505814. Pmcid: PMC4825723.
  • Sun L, Kokura K, Izumi V, Koomen JM, Seto E, Chen J, Fang J. MPP8 and SIRT1 crosstalk in E-cadherin gene silencing and epithelial-mesenchymal transition. EMBO Rep. 2015 Jun;16(6):689-699. Pubmedid: 25870236. Pmcid: PMC4467853.
  • Peng L, Yuan Z, Li Y, Ling H, Izumi V, Fang B, Fukasawa K, Koomen J, Chen J, Seto E. Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival. J Biol Chem. 2015 Apr;290(14):8904-8912. Pubmedid: 25670865. Pmcid: PMC4423681.
  • Chen L, Borcherds W, Wu S, Becker A, Schonbrunn E, Daughdrill GW, Chen J. Autoinhibition of MDMX by intramolecular p53 mimicry. Proc Natl Acad Sci U S A. 2015 Apr;112(15):4624-4629. Pubmedid: 25825738. Pmcid: PMC4403185.
  • Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J, Li C, Gu L, Li GM, Bai W, Wang H, Zhang X. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα. Mol Cell. 2014 Jul;55(1):31-46. Pubmedid: 24882211. Pmcid: PMC4188514.
  • Zheng H, Chen L, Pledger WJ, Fang J, Chen J. p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene. 2014 Feb;33(6):734-744. Pubmedid: 23376847. Pmcid: PMC3912226.
  • Cheng Q, Song T, Chen L, Chen J. Autoactivation of the MDM2 E3 ligase by intramolecular interaction. Mol Cell Biol. 2014 Aug;34(15):2800-2810. Pubmedid: 24842904. Pmcid: PMC4135571.
  • Schneeberger VE, Luetteke N, Ren Y, Berns H, Chen L, Foroutan P, Martinez GV, Haura EB, Chen J, Coppola D, Wu J. SHP2E76K mutant promotes lung tumorigenesis in transgenic mice. Carcinogenesis. 2014 Aug;35(8):1717-1725. Pubmedid: 24480804. Pmcid: PMC4123642.
  • Yang L, Chen J. SirT1 and rRNA in the nucleolus: regulating the regulator. Oncoscience. 2014;1(2):111-112. Pubmedid: 25594003. Pmcid: PMC4278288.
  • Yang L, Song T, Chen L, Kabra N, Zheng H, Koomen J, Seto E, Chen J. Regulation of SirT1-nucleomethylin binding by rRNA coordinates ribosome biogenesis with nutrient availability. Mol Cell Biol. 2013 Oct;33(19):3835-3848. Pubmedid: 23897426. Pmcid: PMC3811878.
  • 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.
  • Song T, Yang L, Kabra N, Chen L, Koomen J, Haura EB, Chen J. The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription. J Biol Chem. 2013 Jul;288(29):20908-20917. Pubmedid: 23737528. Pmcid: PMC3774361.
  • Zheng H, Yang L, Peng L, Izumi V, Koomen J, Seto E, Chen J. hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1. Mol Cell Biol. 2013 Dec;33(24):4960-4970. Pubmedid: 24126058. Pmcid: PMC3889553.
  • 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 δ-tocotrienol induces p27(Kip1)-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism. PLoS One. 2013 Aug;8(2):e52526. Pubmedid: 23393547. Pmcid: PMC3564846.
  • 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 Aug;8(2):e55813. Pubmedid: 23405218. Pmcid: PMC3566025.
  • 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, 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.
  • Wu S, Chen L, Becker A, Schonbrunn E, Chen J. Casein kinase 1α regulates an MDMX intramolecular interaction to stimulate p53 binding. Mol Cell Biol. 2012 Dec;32(23):4821-4832. Pubmedid: 23028042. Pmcid: PMC3497597.
  • 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 May;286(18):16018-16029. Pubmedid: 21454483. Pmcid: PMC3091211.
  • 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.
  • 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 Mar;21(5):1472-1475. Pubmedid: 21277201. Pmcid: PMC3057119.
  • 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.
  • 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.
  • 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 Mar;285(11):8383-8394. Pubmedid: 20068047. Pmcid: PMC2832988.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Li B, Cheng Q, Li Z, Chen J. p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors. Cell Cycle. 2010 Apr;9(7):1411-1420. Pubmedid: 20372076. Pmcid: PMC3008305.
  • 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 May;284(21):13987-14000. Pubmedid: 19321440. Pmcid: PMC2682847.
  • 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 Jul;19(14):3756-3759. Pubmedid: 19457663. Pmcid: PMC2754843.
  • 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.
  • Cheng Q, Chen L, Li Z, Lane WS, Chen J. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. Embo J. 2009 Dec;28(24):3857-3867. Pubmedid: 19816404. Pmcid: PMC2797053.
  • 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.
  • 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 Apr;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.
  • 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. Pmcid: PMC2268405.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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. Pmcid: PMC1679771.
  • 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.
  • 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 Sep;24(18):3279-3290. Pubmedid: 16107876. Pmcid: PMC1224681.
  • 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. 2005 Oct;24(19):3411-3422. Pubmedid: 16163388. Pmcid: PMC1276172.
  • 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.
  • Pan Y, Chen J. Modification of MDMX by sumoylation. Biochem Bioph Res Co. 2005 Jul;332(3):702-709. Pubmedid: 15907800.
  • 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.
  • 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.
  • 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 Aug;22(34):5348-5357. Pubmedid: 12917636.
  • Pan Y, Chen J. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol. 2003 Aug;23(15):5113-5121. Pubmedid: 12860999. Pmcid: PMC165735.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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, Lu W, Chen J. Activation of an MDM2-specific caspase by p53 in the absence of apoptosis. J Biol Chem. 1999 May;274(21):15271-15277. Pubmedid: 10329737.
  • 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 May;19(5):3257-3266. Pubmedid: 10207051.
  • 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 Jan;5(1):21-34. Pubmedid: 10072445.
  • 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 Jan;19(2):232-240. Pubmedid: 10645001.
  • 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. 1998 Nov;17(20):2629-2636. Pubmedid: 9840926 .
  • 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.
  • 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.
  • 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.