High Mdm4 levels suppress p53 activity and enhance its half-life in acute myeloid leukaemia

Oncotarget

Volumn 5, Issue 4, 2014, Pages 933-943

  Tan, Ban Xiong ^a   Khoo, Kian Hoe ^a   Lim, Tit Meng ^b   Lane, David Philip ^a  

^a AGENCY FOR SCIENCE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

AML; Mdm4; p53

Indexed keywords

NUTLIN 3; PROTEIN MDMX; PROTEIN P53; IMIDAZOLE DERIVATIVE; MDM4 PROTEIN, HUMAN; NUCLEAR PROTEIN; ONCOPROTEIN; PIPERAZINE DERIVATIVE; TP53 PROTEIN, HUMAN;

ACUTE GRANULOCYTIC LEUKEMIA; APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOPLASM; DRUG SENSITIVITY; DYNAMICS; FLOW CYTOMETRY; GENETIC MANIPULATION; HALF LIFE TIME; HUMAN; HUMAN CELL; INCUBATION TIME; LEUKEMIA CELL LINE; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN SYNTHESIS INHIBITION; TRANSCRIPTION TERMINATION; WILD TYPE; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETICS; LEUKEMIA, MYELOID, ACUTE; METABOLISM; PATHOLOGY; PHYSIOLOGY; TUMOR CELL LINE;

APOPTOSIS; CELL LINE, TUMOR; HUMANS; IMIDAZOLES; LEUKEMIA, MYELOID, ACUTE; NUCLEAR PROTEINS; PIPERAZINES; PROTO-ONCOGENE PROTEINS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84897409479     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.1559     Document Type: Article

References (49)

1. Vogelstein B, Lane D and Levine AJ. Surfing the p53 network. Nature. 2000; 408(6810):307-310.
2. Moll UM and Petrenko O. The MDM2-p53 interaction. Mol Cancer Res. 2003; 1(14):1001-1008.
3. Kubbutat MHG, Jones SN and Vousden KH. Regulation of p53 stability by Mdm2. Nature. 1997; 387(6630):299-303.
4. Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen AG, Parant J, Lozano G and Yuan Z-M. Mutual Dependence of MDM2 and MDMX in Their Functional Inactivation of p53. Journal of Biological Chemistry. 2002; 277(22):19251-19254.
5. Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven van Oordt W, Hateboer G, van der Eb AJ and Jochemsen AG. MDMX: a novel p53-binding protein with some functional properties of MDM2. The EMBO Journal. 1996; 15(19):5349-5357.
6. Toledo F and Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer. 2006; 6(12):909-923.
7. Pan Y and Chen J. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol. 2003; 23(15):5113-5121.
8. Badciong JC and Haas AL. MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination. J Biol Chem. 2002; 277(51):49668-49675.
9. Wang X, Wang J and Jiang X. MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination. J Biol Chem. 2011; 286(27):23725-23734.
10. Hu G, Zhang W and Deisseroth AB. P53 gene mutations in acute myelogenous leukaemia. British journal of haematology. 1992; 81(4):489-494.
11. Bueso-Ramos CE, Yang Y, deLeon E, McCown P, Stass SA and Albitar M. The human MDM-2 oncogene is overexpressed in leukemias. Blood. 1993; 82(9):2617-2623.
12. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med. 2007; 13(1):23-31.
13. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N and Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004; 303(5659):844-848.
14. Leong SM, Tan BX, Ahmad BB, Yan T, Chee LY, Ang ST, Tay KG, Koh LP, Yeoh AEJ, Koay ES-C, Mok Y-K and Lim TM. Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. Blood. 2010; 116(17):3286-3296.
15. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005; 352(3):254-266.
16. Quentmeier H, Martelli MP, Dirks WG, Bolli N, Liso A, Macleod RA, Nicoletti I, Mannucci R, Pucciarini A, Bigerna B, Martelli MF, Mecucci C, Drexler HG and Falini B. Cell line OCI/AML3 bears exon-12 NPM gene mutation-A and cytoplasmic expression of nucleophosmin. Leukemia. 2005; 19(10):1760-1767.
17. Tiacci E, Spanhol-Rosseto A, Martelli MP, Pasqualucci L, Quentmeier H, Grossmann V, Drexler HG and Falini B. The NPM1 wild-type OCI-AML2 and the NPM1-mutated OCI-AML3 cell lines carry DNMT3A mutations. Leukemia. 2012; 26(3):554-557.
18. van Leeuwen IMM, Higgins M, Campbell J, Brown CJ, McCarthy AR, Pirrie L, Westwood NJ and Laín S. Mechanism-specific signatures for small-molecule p53 activators. Cell Cycle. 2011; 10(10):1590-1598.
19. Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E and Oren M. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 2001; 15(9):1067-1077.
20. Midgley CA, Desterro JM, Saville MK, Howard S, Sparks A, Hay RT and Lane DP. An N-terminal p14ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo. Oncogene. 2000; 19(19):2312-2323.
21. Dayal S, Sparks A, Jacob J, Allende-Vega N, Lane DP and Saville MK. Suppression of the Deubiquitinating Enzyme USP5 Causes the Accumulation of Unanchored Polyubiquitin and the Activation of P53. Journal of Biological Chemistry. 2009; 284(8):5030-5041.
22. Stevenson LF, Sparks A, Allende-Vega N, Xirodimas DP, Lane DP and Saville MK. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. The EMBO Journal. 2007; 26(4):976-986.
23. Ohtsubo C, Shiokawa D, Kodama M, Gaiddon C, Nakagama H, Jochemsen AG, Taya Y and Okamoto K. Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2. Cancer Sci. 2009; 100(7):1291-1299.
24. Danovi D, Meulmeester E, Pasini D, Migliorini D, Capra M, Frenk R, de Graaf P, Francoz S, Gasparini P, Gobbi A, Helin K, Pelicci PG, Jochemsen AG and Marine J-C. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol. 2004; 24(13):5835-5843.
25. Laurie NA, Donovan SL, Shih C-S, Zhang J, Mills N, Fuller C, Teunisse A, Lam S, Ramos Y, Mohan A, Johnson D, Wilson M, Rodriguez-Galindo C, Quarto M, Francoz S, Mendrysa SM, et al. Inactivation of the p53 pathway in retinoblastoma. Nature. 2006; 444(7115):61-66.
26. Gembarska A, Luciani F, Fedele C, Russell EA, Dewaele M, Villar S, Zwolinska A, Haupt S, Lange Jd, Yip D, Goydos J, Haigh JJ, Haupt Y, Larue L, Jochemsen A, Shi H, et al. MDM4 is a key therapeutic target in cutaneous melanoma. Nature Medicine. 2012; 18(8):1239-1247.
27. Zhang and Wang H. MDM2 oncogene as a novel target for human cancer therapy. Current pharmaceutical design. 2000; 6(4):393-416.
28. Stott FJ, Bates S, James MC, McConnell BB, Starborg M, Brookes S, Palmero I, Ryan K, Hara E, Vousden KH and Peters G. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. The EMBO Journal. 1998; 17(17):5001-5014.
29. Di Vizio D, Cito L, Boccia A, Chieffi P, Insabato L, Pettinato G, Motti ML, Schepis F, D'Amico W, Fabiani F, Tavernise B, Venuta S, Fusco A and Viglietto G. Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors. Oncogene. 2005; 24(11):1882-1894.
30. Scheffner M, Werness BA, Huibregtse JM, Levine AJ and Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990; 63(6):1129-1136.
31. Nikolaev AY, Li M, Puskas N, Qin J and Gu W. Parc: a cytoplasmic anchor for p53. Cell. 2003; 112(1):29-40.
32. Houben R, Hesbacher S, Schmid CP, Kauczok CS, Flohr U, Haferkamp S, Muller CS, Schrama D, Wischhusen J and Becker JC. High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays. PLoS ONE. 2011; 6(7):e22096.
33. Koster R, Timmer-Bosscha H, Bischoff R, Gietema JA and de Jong S. Disruption of the MDM2-p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway. Cell death&disease. 2011; 2:e148.
34. Wang X. p53 regulation: Teamwork between RING domains of Mdm2 and MdmX. Cell Cycle. 2011; 10(24):4225-4229.
35. Hu B, Gilkes DM, Farooqi B, Sebti SM and Chen J. MDMX Overexpression Prevents p53 Activation by the MDM2 Inhibitor Nutlin. Journal of Biological Chemistry. 2006; 281(44):33030-33035.
36. Di Conza G, Mancini F, Buttarelli M, Pontecorvi A, Trimarchi F and Moretti F. MDM4 enhances p53 stability by promoting an active conformation of the protein upon DNA damage. Cell Cycle. 2012; 11(4):749-760.
37. Valentin-Vega YA, Barboza JA, Chau GP, El-Naggar AK and Lozano G. High levels of the p53 inhibitor MDM4 in head and neck squamous carcinomas. Hum Pathol. 2007; 38(10):1553-1562.
38. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-607.
39. Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR and Jackson MW. Levels of HdmX Expression Dictate the Sensitivity of Normal and Transformed Cells to Nutlin-3. Cancer Research. 2006; 66(6):3169-3176.
40. Wade M, Wong ET, Tang M, Stommel JM and Wahl GM. Hdmx Modulates the Outcome of P53 Activation in Human Tumor Cells. Journal of Biological Chemistry. 2006; 281(44):33036-33044.
41. Bernal F, Wade M, Godes M, Davis TN, Whitehead DG, Kung AL, Wahl GM and Walensky LD. A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53. Cancer Cell. 2010; 18(5):411-422.
42. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M and Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004; 303(5660):1010-1014.
43. Leu JI, Dumont P, Hafey M, Murphy ME and George DL. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol. 2004; 6(5):443-450.
44. Arima Y, Nitta M, Kuninaka S, Zhang D, Fujiwara T, Taya Y, Nakao M and Saya H. Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria. J Biol Chem. 2005; 280(19):19166-19176.
45. Erster S, Mihara M, Kim RH, Petrenko O and Moll UM. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol Cell Biol. 2004; 24(15):6728-6741.
46. Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C, Pan H, Kessler H, Pancoska P and Moll UM. WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 2006; 281(13):8600-8606.
47. Sot B, Freund SM and Fersht AR. Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the anti-apoptotic BCL-xL. J Biol Chem. 2007; 282(40):29193-29200.
48. Kojima K, McQueen T, Chen Y, Jacamo R, Konopleva M, Shinojima N, Shpall E, Huang X and Andreeff M. p53 activation of mesenchymal stromal cells partially abrogates microenvironment-mediated resistance to FLT3 inhibition in AML through HIF-1alpha-mediated down-regulation of CXCL12. Blood. 2011; 118(16):4431-4439.
49. Stühmer T, Chatterjee M, Hildebrandt M, Herrmann P, Gollasch H, Gerecke C, Theurich S, Cigliano L, Manz RA, Daniel PT, Bommert K, Vassilev LT and Bargou RC. Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma. Blood. 2005; 106(10):3609-3617.