Mdm2 overexpression and p73 loss exacerbate genomic instability and dampen apoptosis, resulting in B-cell lymphoma

Oncogene

Volumn 35, Issue 3, 2016, Pages 358-365

  Riley, M F ^a   You, M J ^a   Multani, A S ^a   Lozano, G ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD19 ANTIGEN; CD45 ANTIGEN; IMMUNOGLOBULIN M; PROTEIN BAX; PROTEIN BCL 2; PROTEIN MDM2; PROTEIN P53; PROTEIN P73; DNA BINDING PROTEIN; MDM2 PROTEIN, HUMAN; NUCLEAR PROTEIN; P73 PROTEIN, HUMAN; TP53 PROTEIN, HUMAN; TRP73 PROTEIN, MOUSE; TUMOR PROTEIN P73; TUMOR SUPPRESSOR PROTEIN;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; B CELL LYMPHOMA; B LYMPHOCYTE; CARCINOGENESIS; CELL AGING; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; CHROMOSOME ABERRATION; CHROMOSOME ANALYSIS; CHROMOSOME BREAKAGE; CONTROLLED STUDY; EMBRYO; FIBROBLAST; GENOMIC INSTABILITY; HETEROZYGOSITY LOSS; METAPHASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; SENESCENCE; SURVIVAL TIME; UPREGULATION; ANIMAL; BIOSYNTHESIS; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; PATHOLOGY; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; APOPTOSIS; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; FIBROBLASTS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMIC INSTABILITY; HUMANS; LYMPHOMA, B-CELL; MICE; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS C-BCL-2; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR PROTEIN P73; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS;

EID: 84955400153     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.88     Document Type: Article

References (36)

1. 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: 203-206.
2. Jones SN, Roe AE, Donehower LA, Bradley A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 1995; 378: 206-208.
3. Wade M, Li YC, Wahl GM. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 2013; 13: 83-96.
4. Lundgren K, Montes de Oca Luna R, McNeill YB, Emerick EP, Spencer B, Barfield CR et al. Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53. Genes Dev 1997; 11: 714-725.
5. Bouska A, Lushnikova T, Plaza S, Eischen CM. Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol 2008; 28: 4862-4874.
6. 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: 15608-15612.
7. Wang P, Lushnikova T, Odvody J, Greiner TC, Jones SN, Eischen CM. Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells. Oncogene 2008; 27: 1590-1598.
8. Lushnikova T, Bouska A, Odvody J, Dupont WD, Eischen CM. Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene 2011; 30: 4622-4631.
9. Riley MF, Lozano G. The many faces of MDM2 binding partners. Genes Cancer 2012; 3: 226-239.
10. Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 2005; 7: 363-373.
11. Zdzalik M, Pustelny K, Kedracka-Krok S, Huben K, Pecak A, Wladyka B et al. Interaction of regulators Mdm2 and Mdmx with transcription factors p53, p63 and p73. Cell Cycle 2010; 9: 4584-4591.
12. Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X et al. MDM2 suppresses p73 function without promoting p73 degradation. Mol Cell Biol 1999; 19: 3257-3266.
13. Balint E, Bates S, Vousden KH. Mdm2 binds p73 alpha without targeting degradation. Oncogene 1999; 18: 3923-3929.
14. Irwin MS, Kaelin WG. p53 family update: p73 and p63 develop their own identities. Cell Growth Differ 2001; 12: 337-349.
15. Jost CA, Marin MC, Kaelin WG Jr.. p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature 1997; 389: 191-194.
16. Du W, Jiang P, Mancuso A, Stonestrom A, Brewer MD, Minn AJ et al. TAp73 enhances the pentose phosphate pathway and supports cell proliferation. Nat Cell Biol 2013; 15: 991-1000.
17. Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung CC et al. TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev 2008; 22: 2677-2691.
18. Wilhelm MT, Rufini A, Wetzel MK, Tsuchihara K, Inoue S, Tomasini R et al. Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway. Genes Dev 2010; 24: 549-560.
19. Grob TJ, Novak U, Maisse C, Barcaroli D, Lüthi AU, Pirnia F et al. Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53. Cell Death Differ 2001; 8: 1213-1223.
20. Martinez-Delgado B, Melendez B, Cuadros M, Jose Garcia M, Nomdedeu J, Rivas C et al. Frequent inactivation of the p73 gene by abnormal methylation or LOH in non-Hodgkin's lymphomas. Int J Cancer 2002; 102: 15-19.
21. Corn PG, Kuerbitz SJ, van Noesel MM, Esteller M, Compitello N, Baylin SB et al. Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5′ CpG island methylation. Cancer Res 1999; 59: 3352-3356.
22. Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H et al. Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. Blood 1999; 94: 1113-1120.
23. Pluta A, Nyman U, Joseph B, Robak T, Zhivotovsky B, Smolewski P. The role of p73 in hematological malignancies. Leukemia 2006; 20: 757-766.
24. Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J et al. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 2000; 404: 99-103.
25. Wu Y, Mehew JW, Heckman CA, Arcinas M, Boxer LM. Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene 2001; 20: 240-251.
26. Findley HW, Gu L, Yeager AM, Zhou M. Expression and regulation of Bcl-2, Bcl-xl, and Bax correlate with p53 status and sensitivity to apoptosis in childhood acute lymphoblastic leukemia. Blood 1997; 89: 2986-2993.
27. Melino G, Bernassola F, Ranalli M, Yee K, Zong WX, Corazzari M et al. p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. J Biol Chem 2004; 279: 8076-8083.
28. Talos F, Nemajerova A, Flores ER, Petrenko O, Moll UM. p73 suppresses polyploidy and aneuploidy in the absence of functional p53. Mol Cell 2007; 27: 647-659.
29. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA et al. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994; 9: 1799-1805.
30. Wang TT, Hursting SD, Perkins SN, Phang JM. Effects of dehydroepiandrosterone and calorie restriction on the Bcl-2/Bax-mediated apoptotic pathway in p53-deficient mice. Cancer Lett 1997; 116: 61-69.
31. Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G. The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci 2000; 113: 1661-1670.
32. Moller MB, Nielsen O, Pedersen NT. Oncoprotein MDM2 overexpression is associated with poor prognosis in distinct non-Hodgkin's lymphoma entities. Mod Pathol 1999; 12: 1010-1016.
33. Watanabe T, Ichikawa A, Saito H, Hotta T. Overexpression of the MDM2 oncogene in leukemia and lymphoma. Leuk Lymphoma 1996; 21: 391-397 color plates XVI following 5.
34. Amin AR, Paul RK, Thakur VS, Agarwal ML. A novel role for p73 in the regulation of Akt-Foxo1a-Bim signaling and apoptosis induced by the plant lectin, concanavalin A. Cancer Res 2007; 67: 5617-5621.
35. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995; 92: 9363-9367.
36. Gostissa M, Bianco JM, Malkin DJ, Kutok JL, Rodig SJ, Morse HC et al. Conditional inactivation of p53 in mature B cells promotes generation of nongerminal center-derived B-cell lymphomas. Proc Natl Acad Sci USA 2013; 110: 2934-2939.