Alternative and aberrant splicing of MDM2 mRNA in human cancer

Cancer Cell

Volumn 2, Issue 1, 2002, Pages 9-15

  Bartel, Frank ^a,b   Taubert, Helge ^b   Harris, Linda C ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; PROTEIN MDM2; PROTEIN P53; TUMOR SUPPRESSOR PROTEIN; ISOPROTEIN; MDM2 PROTEIN, HUMAN; NUCLEAR PROTEIN; ONCOPROTEIN; TUMOR PROTEIN;

CANCER; GENE EXPRESSION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC VARIABILITY; HUMAN; NEUROECTODERM TUMOR; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; RNA SPLICING; TUMOR GROWTH; ALTERNATIVE RNA SPLICING; ANIMAL; BINDING SITE; BIOLOGICAL MODEL; CELL CULTURE; CHEMISTRY; GENETICS; METABOLISM; MUTATION; NEOPLASM; PATHOLOGY; PROGNOSIS;

ALTERNATIVE SPLICING; ANIMALS; BINDING SITES; HUMANS; MODELS, GENETIC; MUTATION; NEOPLASM PROTEINS; NEOPLASMS; NUCLEAR PROTEINS; PROGNOSIS; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, MESSENGER; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53;

EID: 0036655060     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1535-6108(02)00091-0     Document Type: Review

References (59)

1. Argentini, M., Barboule, N., and Wasylyk, B. (2001). The contribution of the acidic domain of MDM2 to p53 and MDM2 stability. Oncogene 20, 1267-1275.
2. Barak, Y., Gottlieb, E., Juven-Gershon, T., and Oren, M. (1994). Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes Dev. 8, 1739-1749.
3. Bartel, F., Meye, A., Wurl, P., Kappler, M., Bache, M., Lautenschlager, C., Grunbaum, U., Schmidt, H., and Taubert, H. (2001). 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, 168-175.
4. Bartel, F., Taylor, A.C., Taubert, H., and Harris, L.C. (2002). Novel mdm2 splice variants identified in pediatric Rhabdomyosarcoma tumors and cell lines. Oncol. Res. 12, 451-457.
5. Brown, D.R., Thomas, C.A., and Deb, S.P. (1998). The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis. EMBO J. 17, 2513-2525.
6. Brown, C.Y., Mize, G.J., Pineda, M., George, D.L., and Morris, D.R. (1999). Role of two upstream open reading frames in the translational control of oncogene mdm2. Oncogene 18, 5631-5637.
7. Bueso-Ramos, C.E., Manshouri, T., Haidar, M.A., Yang, Y., McCown, P., Ordonez, N., Glassman, A., Sneige, N., and Albitar, M. (1996). Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res. Treat. 37, 179-188.
8. Cahilly-Snyder, L., Yang-Reng, T., Francke, U., and George, D.L. (1987). Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat. Cell Mol. Genet. 13, 235-244.
9. Chen, J., Wu, X., Lin, J., and Levine, A.J. (1996). mdm-2 Inhibits the G1 Arrest and Apoptosis Functions of the p53 Tumor Suppressor Protein. Mol. Cell. Biol. 16, 2445-2452.
10. Cordon-Cardo, C., Latres, E., Drobnjak, M., Oliva, M.R., Pollack, D., Woodruff, J.M., Marechal, V., Chen, J., Brennan, M.F., and Levine, A.J. (1994). Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res. 54, 794-799.
11. Dang, J., Kuo, M.L., Eischen, C.M., Stepanova, L., Sherr, C.J., and Roussel, M.F. (2002). The RING domain of Mdm2 can inhibit cell proliferation. Cancer Res. 62, 1222-1230.
12. Dilla, T., Velasco, J.A., Medina, D.L., Gonzalez-Palacios, J.F., and Santisteban, P. (2000). The MDM2 oncoprotein promotes apoptosis in p53-deficient human medullary thyroid carcinoma cells. Endocrinology 141, 420-429.
13. Dubs-Poterszman, M.C., Tocque, B., and Wasylyk, B. (1995). MDM2 transformation in the absence of p53 and abrogation of the p107 G1 cell-cycle arrest. Oncogene 11, 2445-2449.
14. Eischen, C.M., Weber, J.D., Roussel, M.F., Sherr, C.J., and Cleveland, J.L. (1999). Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev. 13, 2658-2669.
15. Evans, S.C., Viswanathan, M., Grier, J.D., Narayana, M., El Naggar, A.K., and Lozano, G. (2001). An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. Oncogene 20, 4041-4049.
16. Evdokiou, A., Atkins, G.J., Bouralexis, S., Hay, S., Raggatt, L.J., Cowled, P.A., Graves, S.E., Clayer, M., and Findlay, D.M. (2001). Expression of alternatively-spliced MDM2 transcripts in giant cell tumours of bone. Int. J. Oncol. 19, 625-632.
17. Fakharzadeh, S.S., Trusko, S.P., and George, D.L. (1991). Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 10, 1565-1569.
18. Folberg-Blum, A., Sapir, A., Shilo, B.Z., and Oren, M. (2002). Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila. Oncogene 21, 2413-2417.
19. Freedman, D.A., Wu, L., and Levine, A.J. (1999). Functions of the MDM2 oncoprotein. Cell. Mol. Life Sci. 55, 96-107.
20. Gustafsson, B., Stal, O., and Gustafsson, B. (1998). Overexpression of MDM2 in acute childhood lymphoblastic leukemia. Pediatr. Hematol. Oncol. 15, 519-526.
21. Haines, D.S., Landers, J.E., Engle, L.J., and George, D.L. (1994). Physical and functional interaction between wild-type p53 and mdm2 proteins. Mol. Cell. Biol. 14, 1171-1178.
22. Higashiyama, M., Doi, O., Kodama, K., Yokouchi, H., Kasugai, T., Ishiguro, S., Takami, K., Nakayama, T., and Nishisho, I. (1997). MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br. J. Cancer 75, 1302-1308.
23. Honda, R., and Yasuda, H. (2000). Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene 19, 1473-1476.
24. Hori, M., Shimazaki, J., Inagawa, S., Itabashi, M., and Hori, M. (2000). Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement. Pathol. Int. 50, 786-792.
25. Haupt, Y., Maya, R., Kazaz, A., and Oren, M. (1997). Mdm2 promotes rapid degradation of p53. Nature 15, 296-299.
26. Jones, S.N., Hancock, A.R., Vogel, H., Donehower, L.A., and Bradley, A. (1998). Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc. Natl. Acad. Sci. USA 95, 15608-15612.
27. Juven-Gershon, T., and Oren, M. (1999). Mdm2: the ups and downs. Mol. Med. 5, 71-83.
28. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., and Shkedy, D. (1999). Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc. Natl. Acad. Sci. USA 96, 14973-14977.
29. Kraus, A., Neff, F., Behn, M., Schuermann, M., Muenkel, K., and Schlegel, J. (1999). Expression of alternatively spliced mdm2 transcripts correlates with stabilized wild-type p53 protein in human glioblastoma cells. Int. J. Cancer 80, 930-934.
30. Kubbutat, M.H., Jones, S.N., and Vousden, K.H. (1997). Regulation of p53 stability by Mdm2. Nature 387, 299-303.
31. Kubbutat, M.H., Ludwig, R.L., Levine, A.J., and Vousden, K.H. (1999). Analysis of the degradation function of Mdm2. Cell Growth Differ. 10, 87-92.
32. Landers, J.E., Haines, D.S., Strauss, J.F., III, and George, D.L. (1994). Enhanced translation: a novel mechanism of mdm2 oncogene overexpression identified in human tumor cells. Oncogene 9, 2745-2750.
33. Landers, J.E., Cassel, S.L., and George, D.L. (1997). Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. Cancer Res. 57, 3562-3568.
34. Lukas, J., Gao, D.Q., Keshmeshian, M., Wen, W.H., Tsao-Wei, D., Rosenberg, S., and Press, M.F. (2001). Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer. Cancer Res. 61, 3212-3219.
35. Matsumoto, R., Tada, M., Nozaki, M., Zhang, C.L., Sawamura, Y., and Abe, H. (1998). Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res. 58, 609-613.
36. Mayo, L.D., Turchi, J.J., and Berberich, S.J. (1997). Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer Res. 57, 5013-5016.
37. Millon, R., Muller, D., Schultz, I., Salvi, R., Ghnassia, J.P., Frebourg, T., Wasylyk, B., and Abecassis, J. (2001). Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance. Oral Oncol. 37, 620-631.
38. Momand, J., Jung, D., Wilczynski, S., and Niland, J. (1998).The MDM2 gene amplification database. Nucleic Acids Res. 26, 3453-3459.
39. Momand, J., Wu, H.H., and Dasgupta, G. (2000). MDM2-master regulator of the p53 tumor suppressor protein. Gene 242, 15-29.
40. Momand, J., Zambetti, G.P., Olson, D.C., George, D., and Levine, A.J. (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69, 1237-1245.
41. Newcomb, E.W., Cohen, H., Lee, S., Bhalla, S.K., Bloom, J., Hayes, R.L., and Miller, D.C. (1998). Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol. 8, 655-667.
42. Oca Luna, R.M., Tabor, A.D., Eberspaecher, H., Hulboy, D.L., Worth, L.L., Colman, M.S., Finlay, C.A., and Lozano, G. (1996). The organization and expression of the mdm2 gene. Genomics 33, 352-357.
43. Oliner, J.D., Kinzler, K.W., Meltzer, P.S., George, D.L., and Vogelstein, B. (1992). Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358, 80-83.
44. Packham, G., and Cleveland, J.L. (1995). c-Myc and apoptosis. Biochim. Biophys. Acta 1242, 11-28.
45. Piette, J., Neel, H., and Marechal, V. (1997). Mdm2: keeping p53 under control. Oncogene 15, 1001-1010.
46. Pinkas, J., Naber, S.P., Butel, J.S., Medina, D., and Jerry, D.J. (1999). Expression of MDM2 during mammary tumorigenesis. Int. J. Cancer 81, 292-298.
47. Schlott, T., Nagel, H., Laskawi, R., Eiffert, H., and Droese, M. (2001). Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland. Pathobiology 69, 67-76.
48. Sherr, C.J. (1998).Tumor surveillance via the ARF-p53 pathway. Genes Dev. 12, 2984-2991.
49. Shieh, S.Y., Ikeda, M., Taya, Y., and Prives, C. (1997). DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91, 325-334.
50. Sigalas, I., Calvert, A.M., Anderson, J.J., Neal, D.E., and Lunec, J. (1996). Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer. Nat. Med. 2, 912-917.
51. Tamborini, E., Della, T.G., Lavarino, C., Azzarelli, A., Carpinelli, P., Pierotti, M.A., and Pilotti, S. (2001). Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas. Int. J. Cancer 92, 790-796.
52. Veldhoen, N., Metcalfe, S., and Milner, J. (1999). A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein. Oncogene 18, 7026-7033.
53. Weber, J.D., Kuo, M.L., Bothner, B.D.E.L., Kriwacki, R.W., Roussel, M.F., and Sherr, C.J. (2000). Cooperative signals governing ARF-mdm2 interaction and nucleolar localization of the complex. Mol. Cell. Biol. 20, 2517-2528.
54. Wu, X., Bayle, J.H., Olson, D., and Levine, A.J. (1993). The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 7, 1126-1132.
55. Wurl, P., Meye, A., Schmidt, H., Lautenschlager, C., Kalthoff, H., Rath, F.W., and Taubert, H. (1998). High prognostic significance of Mdm2/p53 co-overexpression in soft tissue sarcomas of the extremities. Oncogene 16, 1183-1185.
56. Zauberman, A., Barak, Y., Ragimov, N., Levy, N., and Oren, M. (1993). Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 - MDM2 complexes. EMBO J. 12, 2799-2808.
57. Zauberman, A., Flusberg, D., Haupt, Y., Barak, Y., and Oren, M. (1995). A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 23, 2584-2592.
58. Zhu, Q., Yao, J., Wani, G., Wani, M.A., and Wani, A.A. (2001). Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53. Evidence for the role of p300 in integrating ubiquitination and proteolysis. J. Biol. Chem. 276, 29695-29701.
59. Zindy, F., Eischen, C.M., Randle, D.H., Kamijo, T., Cleveland, J.L., Sherr, C.J., and Roussel, M.F. (1998). Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 12, 2424-2433.