MDM2 and MDM4 splicing: An integral part of the cancer spliceome

Frontiers in Bioscience

Volumn 14, Issue 7, 2009, Pages 2647-2656

  Jeyaraj, Selvi C ^a   O'Brien, Dennis M ^a   Chandler, Dawn S ^a,b  

^a THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

Alternative splicing; Cancer; DNA damage; MDM2; MDM4; Review; Splicing

Indexed keywords

MURINAE;

MDM2 PROTEIN, HUMAN; MDM4 PROTEIN, HUMAN; NUCLEAR PROTEIN; ONCOPROTEIN; PROTEIN MDM2;

ALTERNATIVE RNA SPLICING; GENETICS; HUMAN; NEOPLASM; REVIEW;

ALTERNATIVE SPLICING; HUMANS; NEOPLASMS; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2;

EID: 63849157552     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/3402     Document Type: Article

References (54)

1. Fakharzadeh, S. S., S. P. Trusko & D. L. George: Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. Embo J, 10, 1565-9 (1991). (Pubitemid 21905621)
2. Shvarts, A., W. T. Steegenga, N. Riteco, T. van Laar, P. Dekker, M. Bazuine, R. C. van Ham, W. van der Houven van Oordt, G. Hateboer, A. J. van der Eb & A. G. Jochemsen: MDMX: a novel p53-binding protein with some functional properties of MDM2. Embo J, 15, 5349-57 (1996). (Pubitemid 26336217)
3. Haupt, Y., R. Maya, A. Kazaz & M. Oren: Mdm2 promotes the rapid degradation of p53. Nature, 387, 296-9 (1997). (Pubitemid 27220766)
4. Momand, J., G. P. Zambetti, D. C. Olson, D. George & A. J. Levine: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69, 1237-45 (1992).
5. Chen, J., X. Wu, J. Lin & A. J. Levine: mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol Cell Biol, 16, 2445-52 (1996). (Pubitemid 26123766)
6. Honda, R. & H. Yasuda: Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene, 19, 1473-6 (2000). (Pubitemid 30171179)
7. Roth, J., M. Dobbelstein, D. A. Freedman, T. Shenk & A. J. Levine: 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, 17, 554-64 (1998). (Pubitemid 28045495)
8. Elenbaas, B., M. Dobbelstein, J. Roth, T. Shenk & A. J. Levine: The MDM2 oncoprotein binds specifically to RNA through its RING finger domain. Mol Med, 2, 439-51 (1996). (Pubitemid 26271698)
9. Chen, J., V. Marechal & A. J. Levine: Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol, 13, 4107-14 (1993). (Pubitemid 23187639)
10. Oliner, J. D., J. A. Pietenpol, S. Thiagalingam, J. Gyuris, K. W. Kinzler & B. Vogelstein: Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature, 362, 857-60 (1993). (Pubitemid 23132165)
11. Kubbutat, M. H., S. N. Jones & K. H. Vousden: Regulation of p53 stability by Mdm2. Nature, 387, 299-303 (1997). (Pubitemid 27220767)
12. Jones, S. N., A. E. Roe, L. A. Donehower & A. Bradley: Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature, 378, 206-8 (1995).
13. Montes de Oca Luna, R., D. S. Wagner & G. Lozano: Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature, 378, 203-6 (1995).
14. Parant, J. M., V. Reinke, B. Mims & G. Lozano: Organization, expression, and localization of the murine mdmx gene and pseudogene. Gene, 270, 277-83 (2001). (Pubitemid 32525825)
15. Sigalas, I., A. H. Calvert, J. J. Anderson, D. E. Neal & J. Lunec: Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer. Nat Med, 2, 912-7 (1996). (Pubitemid 26296763)
16. Matsumoto, R., M. Tada, M. Nozaki, C. L. Zhang, Y. Sawamura & H. Abe: Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res, 58, 609-13 (1998). (Pubitemid 28099465)
17. Kraus, A., F. Neff, M. Behn, M. Schuermann, K. Muenkel & J. Schlegel: Expression of alternatively splicedmdm2 transcripts correlates with stabilized wild-type p53 protein in human glioblastoma cells. Int J Cancer, 80, 930- 4 (1999). (Pubitemid 29108870)
18. Kraus, A., M. W. Gross, R. Knuechel, K. Munkel, F. Neff & J. Schlegel: Aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53. J Neurosurg, 93, 863-72 (2000). (Pubitemid 32803412)
19. Hori, M., J. Shimazaki, S. Inagawa & M. Itabashi: Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement. Pathol Int, 50, 786-92 (2000).
20. Bartel, F., A. C. Taylor, H. Taubert & L. C. Harris: Novel mdm2 splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines. Oncol Res, 12, 451-7 (2000). (Pubitemid 33791805)
21. Evans, S. C., M. Viswanathan, J. D. Grier, M. Narayana, A. K. El-Naggar & G. Lozano: An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. Oncogene, 20, 4041-9 (2001). (Pubitemid 32681609)
22. Lukas, J., D. Q. Gao, M. Keshmeshian, W. H. Wen, D. Tsao-Wei, S. Rosenberg & M. F. Press: Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer. Cancer Res, 61, 3212-9 (2001). (Pubitemid 32691978)
23. Prodosmo, A., S. Giglio, S. Moretti, F. Mancini, F. Barbi, N. Avenia, G. Di Conza, H. J. Schunemann, L. Pistola, V. Ludovini, A. Sacchi, A. Pontecorvi, E. Puxeddu & F. Moretti: Analysis of human MDM4 variants in papillary thyroid carcinomas reveals new potential markers of cancer properties. J Mol Med (2008).
24. Bartel, F., J. Schulz, A. Bohnke, K. Blumke, M. Kappler, M. Bache, H. Schmidt, P. Wurl, H. Taubert & S. Hauptmann: Significance of HDMX-S (or MDM4) mRNA splice variant overexpression and HDMX gene amplification on primary soft tissue sarcoma prognosis. Int J Cancer, 117, 469-75 (2005). (Pubitemid 41429571)
25. Rallapalli, R., G. Strachan, B. Cho, W. E. Mercer & D. J. Hall: A novel MDMX transcript expressed in a variety of transformed cell lines encodes a truncated protein with potent p53 repressive activity. J Biol Chem, 274, 8299-308 (1999).
26. Dias, C. S., Y. Liu, A. Yau, L. Westrick & S. C. Evans: Regulation of hdm2 by Stress-Induced hdm2alt1 in Tumor and Nontumorigenic Cell Lines Correlating with p53 Stability. Cancer Res, 66, 9467-73 (2006). (Pubitemid 44623644)
27. Dang, J., M. L. Kuo, C. M. Eischen, L. Stepanova, C. J. Sherr & M. F. Roussel: The RING domain of Mdm2 can inhibit cell proliferation. Cancer Res, 62, 1222-30 (2002). (Pubitemid 34160312)
28. Chandler, D. S., R. K. Singh, L. C. Caldwell, J. L. Bitler & G. Lozano: Genotoxic Stress Induces Coordinately Regulated Alternative Splicing of the p53 Modulators MDM2 and MDM4. Cancer Res, 66, 9502-9508 (2006). (Pubitemid 44623648)
29. Zauberman, A., D. Flusberg, Y. Haupt, Y. Barak & M. Oren: A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res, 23, 2584-92 (1995).
30. Lander, E. S., L. M. Linton, B. Birren, C. Nusbaum, M. C. Zody, J. Baldwin, K. Devon, K. Dewar, M. Doyle, W. FitzHugh, R. Funke, D. Gage, K. Harris, A. Heaford, J. Howland, L. Kann, J. Lehoczky, R. LeVine, P. McEwan, K. McKernan, J. Meldrim, J. P. Mesirov, C. Miranda, W. Morris, J. Naylor, C. Raymond, M. Rosetti, . R. Santos, A. Sheridan, C. Sougnez, N. Stange-Thomann, N. Stojanovic, A. Subramanian, D. Wyman, J. Rogers, J. Sulston, R. Ainscough, S. Beck, D. Bentley, J. Burton, C. Clee, N. Carter, A. Coulson, R. Deadman, P. Deloukas, A. Dunham, I. Dunham, R. Durbin, L. French, D. Grafham, S. Gregory, T. Hubbard, S. Humphray, A. Hunt, M. Jones, C. Lloyd, A. McMurray, L. Matthews, S. Mercer, S. Milne, J. C. Mullikin, A. Mungall, R. Plumb, M. Ross, R. Shownkeen, S. Sims, R. H. Waterston, R. K. Wilson, L. W. Hillier, J. D. McPherson, M. A. Marra, E. R. Mardis, L. A. Fulton, A. T. Chinwalla, K. H. Pepin, W. R. Gish, S. L. Chissoe, M. C. Wendl, K. D. Delehaunty, T. L. Miner, A. Delehaunty, J. B. Kramer, L. L. Cook, R. S. Fulton, D. L. Johnson, P. J. Minx, S. W. Clifton, T. Hawkins, E. Branscomb, P. Predki, P. Richardson, S. Wenning, T. Slezak, N. Doggett, J. F. Cheng, A. Olsen, S. Lucas, C. Elkin, E. Uberbacher, M. Frazier, R. A. Gibbs, D. M. Muzny, S. E. Scherer, J. B. Bouck, E. J. Sodergren, K. C. Worley, C. M. Rives, J. H. Gorrell, M. L. Metzker, S. L. Naylor, R. S. Kucherlapati, D. L. Nelson, G. M. Weinstock, Y. Sakaki, A. Fujiyama, M., Hattori, T. Yada, A. Toyoda, T. Itoh, C. Kawagoe, H. Watanabe, Y. Totoki, T. Taylor, J. Weissenbach, R. Heilig, W. Saurin, F. Artiguenave, P. Brottier, T. Bruls, E. Pelletier, C. Robert, P. Wincker, D. R. Smith, L. Doucette- Stamm, M. Rubenfield, K. Weinstock, H. M. Lee, J. Dubois, A. Rosenthal, M. Platzer, G. Nyakatura, S. Taudien, A. Rump, H. Yang, J. Yu, J. Wang, G. Huang, J. Gu, L. Hood, L. Rowen, A. Madan, S. Qin, R. W. Davis, N. A. Federspiel, A. P. Abola, M. J. Proctor, R. M. Myers, J. Schmutz, M. Dickson, J. Grimwood, D. R. Cox, M. V. Olson, R. Kaul, C. Raymond, N. Shimizu, K. Kawasaki, S. Minoshima, G. A. Evans, M. Athanasiou, R. Schultz, B. A. Roe, F. Chen, H. Pan, J. Ramser, H. Lehrach, R. Reinhardt, W. R. McCombie, M. de la Bastide, N. Dedhia, H. Blocker, K. Hornischer, G. Nordsiek, R. Agarwala, L. Aravind, J. A. Bailey, A. Bateman, S. Batzoglou, E. Birney, P. Bork, D. G. Brown, C. B. Burge, L. Cerutti, H. C. Chen, D. Church, M. Clamp, R. R. Copley, T. Doerks, S. R. Eddy, E. E. Eichler, T. S. Furey, J. Galagan, J. G. Gilbert, C. Harmon, Y. Hayashizaki, D. Haussler, H. Hermjakob, K. Hokamp, W. Jang, L. S. Johnson, T. A. Jones, S. Kasif, A. Kaspryzk, S. Kennedy, W. J. Kent, P. Kitts, E. V. Koonin, I. Korf, D. Kulp, D. Lancet, T. M. Lowe, A. McLysaght, T. Mikkelsen, J. V. Moran, N. Mulder, V. J. Pollara, C. P. Ponting, G. Schuler, J. Schultz, G. Slater, A. F. Smit, E. Stupka, J. Szustakowski, D. Thierry-Mieg, J. Thierry-Mieg, L. Wagner, J. Wallis, R. Wheeler, A. Williams, Y. I. Wolf, K. H. Wolfe, S. P. Yang, R. F. Yeh, F. Collins, M. S. Guyer, J. Peterson, A. Felsenfeld, K. A. Wetterstrand, A. Patrinos, M. J. Morgan, P. de Jong, J. J. Catanese, K. Osoegawa, H. Shizuya, S. Choi & Y. J. Chen: Initialsequencing and analysis of the human genome. Nature, 409, 860-921 (2001).
31. Hastings, M. L., N. Resta, D. Traum, A. Stella, G. Guanti & A. R. Krainer: An LKB1 AT-AC intron mutation causes Peutz-Jeghers syndrome via splicing at noncanonical cryptic splice sites. Nat Struct Mol Biol, 12, 54-9 (2005). (Pubitemid 40082917)
32. Chen, L. L., M. Sabripour, E. F. Wu, V. G. Prieto, G. N. Fuller & M. L. Frazier: A mutation-created novel intraexonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors. Oncogene, 24, 4271-80 (2005). (Pubitemid 40961780)
33. Mazoyer, S., N. Puget, L. Perrin-Vidoz, H. T. Lynch, O. M. Serova-Sinilnikova & G. M. Lenoir: A BRCA1 nonsense mutation causes exon skipping. Am J Hum Genet, 62, 713-5 (1998). (Pubitemid 28164630)
34. Konig, H., H. Ponta & P. Herrlich: Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator. Embo J, 17, 2904-13 (1998).
35. Ghigna, C., S. Giordano, H. Shen, F. Benvenuto, F. Castiglioni, P. M. Comoglio, M. R. Green, S. Riva & G. Biamonti: Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell, 20, 881-90 (2005). (Pubitemid 41814877)
36. Radisky, D. C., D. D. Levy, L. E. Littlepage, H. Liu, C. M. Nelson, J. E. Fata, D. Leake, E. L. Godden, D. G. Albertson, M. A. Nieto, Z. Werb & M. J. Bissell: Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature, 436, 123-7 (2005). (Pubitemid 40966197)
37. Olson, D. C., V. Marechal, J. Momand, J. Chen, C. Romocki & A. J. Levine: Identification and characterization of multiple mdm-2 proteins and mdm-2- p53 protein complexes. Oncogene, 8, 2353-60 (1993). (Pubitemid 23252363)
38. Haines, D. S., J. E. Landers, L. J. Engle & D. L. George: Physical and functional interaction between wildtype p53 and mdm2 proteins. Mol Cell Biol, 14, 1171-8 (1994). (Pubitemid 24036568)
39. de Oca Luna, R. M., A. D. Tabor, H. Eberspaecher, D. L. Hulboy, L. L. Worth, M. S. Colman, C. A. Finlay & G. Lozano: The organization and expression of the mdm2 gene. Genomics, 33, 352-7 (1996). (Pubitemid 26159851)
40. Eischen, C. M., J. D. Weber, M. F. Roussel, C. J. Sherr & J. L. Cleveland: Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev, 13, 2658-69 (1999). (Pubitemid 29508553)
41. Pinkas, J., S. P. Naber, J. S. Butel, D. Medina & D. J. Jerry: Expression of MDM2 during mammary tumorigenesis. Int J Cancer, 81, 292-8 (1999). (Pubitemid 29144761)
42. Bueso-Ramos, C. E., T. Manshouri, M. A. Haidar, Y. O. Huh, M. J. Keating & M. Albitar: Multiple patterns of MDM-2 deregulation in human leukemias: implications in leukemogenesis and prognosis. Leuk Lymphoma, 17, 13-8 (1995).
43. Bueso-Ramos, C. E., T. Manshouri, M. A. Haidar, Y. Yang, P. McCown, N. Ordonez, A. Glassman, N. Sneige & M. Albitar: Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat, 37, 179-88 (1996). (Pubitemid 26030095)
44. Bartel, F., A. Meye, P. Wurl, M. Kappler, M. Bache, C. Lautenschlager, U. Grunbaum, H. Schmidt & H. Taubert: Amplification of the MDM2 gene, but not expression of splice variants of MDM2 MRNA, is associated with prognosis in soft tissue sarcoma. Int J Cancer, 95, 168-75 (2001). (Pubitemid 32477232)
45. Chandler, D.: Splicing of the p53 pathway. In: Alternative Splicing in Cancer. Ed: J. Venables. Transworld Research Network, Newcastle upon Tyne, UK (2007).
46. Tamborini, E., G. Della Torre, C. Lavarino, A. Azzarelli, P. Carpinelli, M. A. Pierotti & S. Pilotti: Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas. Int J Cancer, 92, 790-6 (2001). (Pubitemid 32467366)
47. Cocquet, J., A. Chong, G. Zhang & R. A. Veitia: Reverse transcriptase template switching and false alternative transcripts. Genomics, 88, 127-31 (2006). (Pubitemid 44183763)
48. Roy, S. W. & M. Irimia: When good transcripts go bad: artifactual RT-PCR 'splicing' and genome analysis. Bioessays, 30, 601-5 (2008). (Pubitemid 351859416)
49. Giglio, S., F. Mancini, F. Gentiletti, G. Sparaco, L. Felicioni, F. Barassi, C. Martella, A. Prodosmo, S. Iacovelli, F. Buttitta, A. Farsetti, S. Soddu, A. Marchetti, A. Sacchi, A. Pontecorvi & F. Moretti: Identification of an aberrantly spliced form of HDMX in human tumors: a new mechanism for HDM2 stabilization. Cancer Res, 65, 9687-94 (2005). (Pubitemid 41541444)
50. de Graaf, P., N. A. Little, Y. F. Ramos, E. Meulmeester, S. J. Letteboer & A. G. Jochemsen: Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2. J Biol Chem, 278, 38315-24 (2003). (Pubitemid 37221723)
51. Momand, J., D. Jung, S. Wilczynski & J. Niland: The MDM2 gene amplification database. Nucleic Acids Res, 26, 3453-9 (1998). (Pubitemid 28347214)
52. Bartel, F., H. Taubert & L. C. Harris: Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell, 2, 9-15 (2002). (Pubitemid 41043984)
53. Sanchez-Aguilera, A., J. F. Garcia, M. Sanchez-Beato & M. A. Piris: Hodgkin's lymphoma cells express alternatively spliced forms of HDM2 with multiple effects on cell cycle control. Oncogene, 25, 2565-74 (2006).
54. Bouska, A., T. Lushnikova, S. Plaza & C. M. Eischen: Mdm2 Promotes Genetic Instability and Transformation Independent of p53. Mol Cell Biol (2008).