Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

MDM2 (Murine Double Minute 2)

  • Scott Bang
  • Heeruk C. Bhatt
  • Yun Yue Chen
  • Manabu KurokawaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101574


Historical Background

Mdm2 (murine double minute 2) was first discovered as one of two gene products that were amplified in the spontaneously transformed mouse 3T3-DM cell line (Cahilly-Snyder et al. 1987). Human MDM2 was subsequently cloned by screening a human cDNA library with the mouse Mdm2 probe (Oliner et al. 1992). Mdm2-overexpressing NIH-3T3 and Rat2 fibroblast cells formed tumors when subcutaneously injected into nude mice, indicating the tumorigenic potential of Mdm2 (Fakharzadeh et al. 1991). Supporting this notion, the MDM2 gene was found to be amplified in sarcomas when it was first cloned (Oliner et al. 1992). Similarly, MDM2 overexpression and amplification were observed in other cancer types, including a subset of lymphoma (Watanabe et al. 1996). Later, it was shown that MDM2 formed a complex with p53, suppressing p53’s tumor suppressor functions (Momand et al. 1992; Oliner et...
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The authors acknowledge support from an NCI Career Development Award R00 CA140948 (to M.K.), American Cancer Society Institutional Research Grant IRG-82-003-30 (to M.K.), a Norris Cotton Cancer Center Prouty Grant (to M.K.), a Norris Cotton Cancer Center Leukemia/Lymphoma Fund (to M.K.), and Waterhouse Research Award (to Y.Y.C.).


  1. Barak Y, Juven T, Haffner R, Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J. 1993;12:461–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Biderman L, Manley JL, Prives C. Mdm2 and MdmX as regulators of gene expression. Genes Cancer. 2012;3:264–73.  https://doi.org/10.1177/1947601912455331.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Blattner C, Hay T, Meek DW, Lane DP. Hypophosphorylation of Mdm2 augments p53 stability. Mol Cell Biol. 2002;22:6170–82.  https://doi.org/10.1128/MCB.22.17.6170-6182.2002.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004;119:591–602.  https://doi.org/10.1016/j.cell.2004.11.022.CrossRefPubMedGoogle Scholar
  5. Boyd SD, Tsai KY, Jacks T. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53. Nat Cell Biol. 2000a;2:563–8.  https://doi.org/10.1038/35023500.CrossRefPubMedGoogle Scholar
  6. Burgess A, Chia KM, Haupt S, Thomas D, Haupt Y, Lim E. Clinical overview of MDM2/X-targeted therapies. Front Oncol. 2016;6:7.  https://doi.org/10.3389/fonc.2016.00007.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cahilly-Snyder L, Yang-Feng T, Francke U, George DL. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3 T3 cell line. Somat Cell Mol Genet. 1987;13:235–44.  https://doi.org/10.1007/BF01535205.CrossRefPubMedGoogle Scholar
  8. Chen J, Marechal VI, Levine AJ. Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol. 1993;13:4107–14.  https://doi.org/10.1128/MCB.13.7.4107.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cheng Q, Chen L, Li Z, Lane WS, Chen J. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J. 2009;28:3857–67.  https://doi.org/10.1038/emboj.2009.294.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cheng Q, Cross B, Li B, Chen L, Li Z, Chen J. Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage. Mol Cell Biol. 2011;31:4951–63.  https://doi.org/10.1128/MCB.05553-11.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cummins JM, Rago C, Kohli M, Kinzler KW, Lengauer C, Vogelstein B. Tumour suppression: disruption of HAUSP gene stabilizes p53. Nature. 2004;428:1.  https://doi.org/10.1038/nature02501.CrossRefPubMedCentralPubMedGoogle Scholar
  12. Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M, Dal Cin P, Maestro R, Fletcher CD, Tallini G. Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. J Pathol. 2000;190:531–6.  https://doi.org/10.1002/(SICI)1096-9896(200004)190:5<531::AID-PATH579>3.0.CO;2-W.CrossRefPubMedGoogle Scholar
  13. Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 1991;10:1565–9.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Feng J, Tamaskovic R, Yang Z, Brazil DP, Merlo A, Hess D, Hemmings BA. Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation. J Biol Chem. 2004;279:35510–7.  https://doi.org/10.1074/jbc.M404936200.CrossRefPubMedGoogle Scholar
  15. Ganguli G, Wasylyk B. p53-Independent functions of MDM2. Mol Cancer Res 2003;1:1027–1035.Google Scholar
  16. Gannon HS, Woda BA, Jones SN. ATM Phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice. Cancer Cell. 2012;21:668–79.  https://doi.org/10.1016/j.ccr.2012.04.011.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Geyer RK, Zhong KY, Maki CG. The MDM2 RING-finger domain is required to promote p53 nuclear export. Nat Cell Biol. 2000;2:569–73.  https://doi.org/10.1038/35023507.CrossRefPubMedGoogle Scholar
  18. Goldberg Z, Sionov RV, Berger M, Zwang Y, Perets R, Van Etten RA, Oren M, Taya Y, Haupt Y. Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation. EMBO J. 2002;21:3715–27.  https://doi.org/10.1093/emboj/cdf384.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature. 1997;387:296–9.  https://doi.org/10.1038/387296a0.CrossRefPubMedGoogle Scholar
  20. He Y, Tollini L, Kim TH, Itahana Y, Zhang Y. The anaphase-promoting complex/cyclosome is an E3 ubiquitin ligase for Mdm2. Cell Cycle. 2014;13:2101–9.  https://doi.org/10.4161/cc.29106.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Herman AG, Hayano M, Poyurovsky MV, Shimada K, Skouta R, Prives C, Stockwell BR. Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination assay. Cancer Discov. 2011;1:312–25.  https://doi.org/10.1158/2159-8290.CD-11-0104.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Honda R, Yasuda H. Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J. 1999;18:22–7.  https://doi.org/10.1093/emboj/18.1.22.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Honda R, Yasuda H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene. 2000;19:1473–6.  https://doi.org/10.1038/sj.onc.1203464.CrossRefPubMedGoogle Scholar
  24. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997;420:25–7.  https://doi.org/10.1016/S0014-5793(97)01480-4.CrossRefPubMedGoogle Scholar
  25. Huang L, Yan Z, Liao X, Li Y, Yang J, Wang ZG, Zuo Y, Kawai H, Shadfan M, Ganapathy S, Yuan ZM. The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo. Proc Natl Acad Sci USA. 2011;108:12001–6.  https://doi.org/10.1073/pnas.1102309108.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav G, Asara J, Xiao Z-XJ, Kaelin WG, Harper JW, Wei W. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCFbeta-TRCP ubiquitin ligase. Cancer Cell. 2010;18:147–59.  https://doi.org/10.1016/j.ccr.2010.06.015.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Itahana K, Mao H, Jin A, Itahana Y, Clegg HV, Lindström MS, Bhat KP, Godfrey VL, Evan GI, Zhang Y. Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell. 2007;12:355–66.  https://doi.org/10.1016/j.ccr.2007.09.007.CrossRefPubMedGoogle Scholar
  28. Jones SN, Roe AE, Donehower LA, Bradley A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature. 1995;378:206–8.  https://doi.org/10.1038/378206a0.CrossRefPubMedGoogle Scholar
  29. Jones SN, Hancock AR, Vogel H, Donehower LA, Bradley A. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci USA. 1998;95:15608–12.  https://doi.org/10.1073/pnas.95.26.15608.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kawai H, Wiederschain D, Yuan ZM. Critical contribution of the MDM2 acidic domain to p53 ubiquitination. Mol Cell Biol. 2003;23:4939–47.  https://doi.org/10.1128/MCB.23.14.4939-4947.2003.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Korkolopoulou P, Christodoulou P, Kouzelis K, Hadjiyannakis M, Priftis A, Stamoulis G, Seretis A, Thomas-Tsagli E. MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor. Br J Cancer. 1997;75:1269–78.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 2015;16:393–405.  https://doi.org/10.1038/nrm4007.CrossRefPubMedGoogle Scholar
  33. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature. 1997;387:299–303.  https://doi.org/10.1038/387299a0.CrossRefPubMedGoogle Scholar
  34. Kurokawa M, Kim J, Geradts J, Matsuura K, Liu L, Ran X, Xia W, Ribar TJ, Henao R, Dewhirst MW, Kim WJ. A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53. Sci Signal. 2013;6:ra32.  https://doi.org/10.1126/scisignal.2003741.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Li J, Kurokawa M. Regulation of MDM2 stability after DNA damage. J Cell Physiol. 2015;230:2318–27.  https://doi.org/10.1002/jcp.24994.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W. Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science. 2003;302:1972–5.  https://doi.org/10.1126/science.1091362.CrossRefPubMedGoogle Scholar
  37. Linares LK, Kiernan R, Triboulet R, Chable-Bessia C, Latreille D, Cuvier O, Lacroix M, Le Cam L, Coux O, Benkirane M. Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol. 2007;9:331–8.  https://doi.org/10.1038/ncb1545.CrossRefPubMedGoogle Scholar
  38. Liu Y, He Y, Jin A, Tikunov AP, Zhou L, Tollini LA, Leslie P, Kim TH, Li LO, Coleman RA, Gu Z. Ribosomal protein–Mdm2–p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation. Proc Natl Acad Sci USA. 2014;111:E2414–22.  https://doi.org/10.1073/pnas.1315605111.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Lu X, Ma O, Nguyen TA, Jones SN, Oren M, Donehower LA. The Wip1 phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory Loop. Cancer Cell. 2007;12:342–54.  https://doi.org/10.1016/j.ccr.2007.08.033.CrossRefPubMedGoogle Scholar
  40. Malonia SK, Dutta P, Santra MK, Green MR. F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress. Proc Natl Acad Sci USA. 2015;112:8632–7.  https://doi.org/10.1073/pnas.1510929112.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Mayo LD, Turchi JJ, Berberich SJ. Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer Res. 1997;57:5013–6.PubMedGoogle Scholar
  42. Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003;1:1001–8.PubMedGoogle Scholar
  43. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992;69:1237–45.  https://doi.org/10.1016/0092-8674(92)90644-R.CrossRefGoogle Scholar
  44. Montes de Oca Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature. 1995;378:203–6.  https://doi.org/10.1038/378203a0.CrossRefPubMedGoogle Scholar
  45. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992;358:80–3.  https://doi.org/10.1038/358080a0.CrossRefPubMedGoogle Scholar
  46. Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993;362:857–60.  https://doi.org/10.1038/362857a0.CrossRefPubMedGoogle Scholar
  47. Pant V, Xiong S, Iwakuma T, Quintás-Cardama A, Lozano G. Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc Natl Acad Sci USA. 2011;108:11995–2000.  https://doi.org/10.1073/pnas.1102241108.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Perry ME, Piette J, Zawadzki JA, Harvey D, Levine AJ. The mdm-2 gene is induced in response to UV light in a p53-dependent manner. Proc Natl Acad Sci USA. 1993;90:11623–7.  https://doi.org/10.1073/pnas.90.24.11623.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Phillips CL, Gerbing R, Alonzo T, Perentesis JP, Harley IT, Meshinchi S, Bhatla D, Radloff G, Davies SM. MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2010;55:248–53.  https://doi.org/10.1002/pbc.22519.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Post SM, Pant V, Abbas H, Quintás-Cardama A. Prognostic impact of the MDM2SNP309 allele in leukemia and lymphoma. Oncotarget. 2010;1:168–74.  https://doi.org/10.18632/oncotarget.100712.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Riley MF, Lozano G. The many faces of MDM2 binding partners. Genes Cancer. 2012;3:226–39.  https://doi.org/10.1177/1947601912455322.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Roth J, Dobbelstein M, Freedman DA, Shenk T, Levine AJ. Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein. EMBO J. 1998;17:554–64.  https://doi.org/10.1093/emboj/17.2.554.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Roxburgh P, Hock AK, Dickens MP, Mezna M, Fischer PM, Vousden KH. Small molecules that bind the Mdm2 RING stabilize and activate p53. Carcinogenesis. 2012;33:791–8.  https://doi.org/10.1093/carcin/bgs092.CrossRefPubMedGoogle Scholar
  54. Sherr CJ. Divorcing ARF and p53: an unsettled case. Nat Rev Cancer. 2006;6:663–73.  https://doi.org/10.1038/nrc1954.CrossRefPubMedGoogle Scholar
  55. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 1997;91:325–34.  https://doi.org/10.1016/S0092-8674(00)80416-X.CrossRefGoogle Scholar
  56. Shinozaki T, Nota A, Taya Y, Okamoto K. Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export. Oncogene. 2003;22:8870–80.  https://doi.org/10.1038/sj.onc.1207176.CrossRefPubMedGoogle Scholar
  57. Singh RK, Iyappan S, Scheffner M. Hetero-oligomerization with MdmX rescues the ubiquitin/Nedd8 ligase activity of RING finger mutants of Mdm2. J Biol Chem. 2007;282:10901–7.  https://doi.org/10.1074/jbc.M610879200.CrossRefPubMedGoogle Scholar
  58. Stad R, Little NA, Xirodimas DP, Frenk R, van der Eb AJ, Lane DP, Saville MK, Jochemsen AG. Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms. EMBO Rep. 2001;2:1029–34.  https://doi.org/10.1093/embo-reports/kve227.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Stevenson LF, Sparks A, Allende-Vega N, Xirodimas DP, Lane DP, Saville MK. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J. 2007;26:976–86.  https://doi.org/10.1038/sj.emboj.7601567.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Stommel JM, Wahl GM. Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation. EMBO J. 2004;23:1547–56.  https://doi.org/10.1038/sj.emboj.7600145.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Tao W, Levine AJ. Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53. Proc Natl Acad Sci USA. 1999a;96:3077–80.  https://doi.org/10.1073/pnas.96.6.3077.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Tao W, Levine AJ. p19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad Sci USA. 1999b;96:6937–41.  https://doi.org/10.1073/pnas.96.12.6937.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Tollini LA, Jin A, Park J, Zhang Y. Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage. Cancer Cell. 2014;26:235–47.  https://doi.org/10.1016/j.ccr.2014.06.006.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303:844–8.  https://doi.org/10.1126/science.1092472.CrossRefPubMedGoogle Scholar
  65. Watanabe T, Hotta T, Ichikawa A, Kinoshita T, Nagai H, Uchida T, Murate T, Saito H. The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. Blood. 1994;84:3158–65.PubMedGoogle Scholar
  66. Watanabe T, Ichikawa A, Saito H, Hotta T. Overexpression of the MDM2 oncogene in leukemia and lymphoma. Leuk Lymphoma. 1996;21:391–7.  https://doi.org/10.3109/10428199609093436.CrossRefPubMedGoogle Scholar
  67. Weber JD, Taylor LJ, Roussel MF, Sherr CJ, Bar-Sagi D. Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol. 1999;1:20–6.  https://doi.org/10.1038/8991.CrossRefPubMedGoogle Scholar
  68. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, Fersht AR. The central region of HDM2 provides a second binding site for p53. Proc Natl Acad Sci USA. 2006;103:1227–32.  https://doi.org/10.1073/pnas.0510343103.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Zhang Y, Lu H. Signaling to p53: ribosomal proteins find their way. Cancer Cell. 2009;16:369–77.  https://doi.org/10.1016/j.ccr.2009.09.024.CrossRefPubMedPubMedCentralGoogle Scholar
  70. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung MC. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol. 2001;3:973–82.  https://doi.org/10.1038/ncb1101-973.CrossRefPubMedGoogle Scholar
  71. Zhuo W, Zhang L, Ling J, Zhu B, Chen Z. MDM2 SNP309 variation contributes to leukemia risk: meta-analyses based on 7259 subjects. Leuk Lymphoma. 2012;53:2245–52.  https://doi.org/10.3109/10428194.2012.691485.CrossRefPubMedGoogle Scholar
  72. Zou Q, Jin J, Hu H, Li HS, Romano S, Xiao Y, Nakaya M, Zhou X, Cheng X, Yang P, Lozano G. USP15 stabilizes MDM2 to mediate cancer cell survival and inhibit antitumor T cell responses. Nat Immunol. 2014;15:562–70.  https://doi.org/10.1038/ni.2885.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Scott Bang
    • 1
  • Heeruk C. Bhatt
    • 1
  • Yun Yue Chen
    • 1
  • Manabu Kurokawa
    • 1
    • 2
    Email author
  1. 1.Department of Molecular and Systems BiologyGeisel School of Medicine at DartmouthHanoverUSA
  2. 2.Norris Cotton Cancer CenterLebanonUSA