MDM2-A, a common Mdm2 splice variant, causes perinatal lethality, reduced longevity and enhanced senescence

DMM Disease Models and Mechanisms

Volumn 2, Issue 1-2, 2009, Pages 47-55

  Volk, Erin L ^a   Schuster, Katja ^b   Nemeth, Katie M ^a   Fan, Liying ^a   Harris, Linda C ^a  

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

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; LUCIFERASE; PROTEIN MDM2; PROTEIN MDM2 A; PROTEIN P21; PROTEIN P53; UNCLASSIFIED DRUG; MDM2 PROTEIN, MOUSE;

AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY MASS; CONTROLLED STUDY; EMBRYO; FIBROBLAST; GENE DOSAGE; GENOTYPE; GROWTH CURVE; IMMUNOPRECIPITATION; KAPLAN MEIER METHOD; LONGEVITY; MOUSE; NEWBORN; NONHUMAN; NUCLEOTIDE SEQUENCE; ORGAN WEIGHT; PERINATAL DEATH; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SENESCENCE; TRANSGENIC MOUSE; WESTERN BLOTTING; WILD TYPE; ALTERNATIVE RNA SPLICING; ANIMAL; CELL AGING; CELL LINE; DISEASE MODEL; GENETICS; HOMOZYGOTE; HUMAN; METABOLISM;

MUS; MUS MUSCULUS;

ALTERNATIVE SPLICING; ANIMALS; CELL AGING; CELL LINE; DISEASE MODELS, ANIMAL; FIBROBLASTS; GENOTYPE; HOMOZYGOTE; HUMANS; LONGEVITY; MICE; MICE, TRANSGENIC; PHENOTYPE; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 67649589120     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.000992     Document Type: Article

References (43)

1. Bartel, F., Taubert, H. and Harris, L. C. (2002a). Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2, 9-15.
2. Bartel, F., Taylor, A. C., Taubert, H. and Harris, L. C. (2002b). Novel mdm2 splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines. Oncol. Res. 12, 451-457.
3. Bartel, F., Pinkert, C. A., Fiedler, W., Wurl, P., Schmidt, H. and Taubert, H. (2004). Expression of alternatively and aberrantly spliced transcripts of the MDM2 mRNA is not tumor-specific. Int. J. Cancer 24, 143-151.
4. Bouvard, V., Zaitchouk, T., Vacher, M., Duthu, A., Canivet, M., Choisy-Rossi, C., Nieruchalski, M. and May, E. (2000). Tissue and cell-specific expression of the p53-target genes: bax, fas, mdm2 and waf1/p21, before and following ionising irradiation in mice. Oncogene 19, 649-660.
5. Campisi, J. (2001). Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 11, S27-S31.
6. Corvi, R., Savelyeva, L., Breit, S., Wenzel, A., Handgretinger, R., Barak, J., Oren, M., Amler, L. and Schwab, M. (1995). Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma. Oncogene 10, 1081-1086.
7. Dang, J., Kuo, M. L., Eischen, C., Stepanova, L., Sherr, C. and Roussel, M. (2002). The RING domain of Mdm2 can inhibit cell proliferation. Cancer Res. 62, 1222-1230.
8. Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O. et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. USA 92, 9363-9367.
9. Donehower, L. A. (2002). Does p53 affect organismal aging? J. Cell Physiol. 192, 23-33.
10. Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Jr, Butel, J. S. and Bradley, A. (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215-221.
11. El-Deiry, W. S., Harper, J. W., O'Conner, P. M., Velculescu, V. E., Canman, C. E., Jackman, J., Pietenpol, J. A., Burrell, M., Hill, D. E., Wang, Y. et al. (1994). WAF1/CIP1 is induced upon p53-mediated growth arrest and apoptosis. Cancer Res. 54, 1169-1174.
12. 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.
13. 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.
14. Fridman, J. S., Hernando, E., Hemann, M. T., de Stanchina, E., Cordon-Cardo, C. and Lowe, S. W. (2003). Tumor promotion by Mdm2 splice variants unable to bind p53. Cancer Res. 63, 5703-5706.
15. Garcia-Cao, I., Garcia-Cao, M., Martin-Caballero, J., Criado, L. M., Klatt, P., Flores, J. M., Weill, J. C., Blasco, M. A. and Serrano, M. (2002). "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 21, 6225-6235.
16. Harvey, M., Sands, A. T., Weiss, R. S., Hegi, M. E., Wiseman, R. W., Pantazis, P., Giovanella, B. C., Tainsky, M. A., Bradley, A. and Donehower, L. A. (1993). In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice. Oncogene 8, 2457-2467.
17. Haupt, Y., Maya, R., Kazaz, A. and Oren, M. (1997). Mdm2 promotes the rapid degradation of p53. Nature 387, 296-299.
18. Hogan, B., Beddington, R., Costnatini, F. and Lacy, E. (1994). Manipulating the Mouse Embryo: A Laboratory Manual. Plainview, NY: Cold Spring Harbor Laboratory Press.
19. Honda, R., Tanaka, H. and Yasuda, H. (1997). Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420, 25-27.
20. Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T. and Weinberg, R. A. (1994). Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1-7.
21. Jones, S. N., Roe, A. E., Donehower, L. A. and Bradley, A. (1995). Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378, 206-208.
22. Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B. and Craig, R. W. (1991). Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51, 6304-6311.
23. Kubbutat, M. H., Jones, S. N. and Vousden, K. H. (1997). Regulation of p53 stability by Mdm2. Nature 387, 299-303.
24. Ladanyi, M., Cha, C., Lewis, R., Jhanwar, S. C., Huvos, A. G. and Healey, J. H. (1993). MDM2 gene amplification in metastatic osteosarcoma. Cancer Res. 53, 16-18.
25. Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R. and Gu, W. (2003). Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science 302, 1972-1975.
26. Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., Sutherland, A., Thorner, M. and Scrable, H. (2004). Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18, 306-319.
27. McKenzie, P. P., McPake, C. R., Ashford, A. A., Vanin, E. F. and Harris, L. C. (2002). MDM2 does not influence p53-mediated sensitivity to DNA-damaging drugs. Mol. Cancer Ther. 1, 1097-1104.
28. Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A. and Perry, M. E. (2006). Tumor suppression and normal aging in mice with constitutively high p53 activity. Genes Dev. 20, 16-21.
29. Miyashita, T. and Reed, J. C. (1995). Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293-299.
30. Momand, J., Zambetti, G. P., Olson, D. C., George, D. and Levine, A. J. (1992). The MDM2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69, 1237-1245.
31. Montes de Oca Luna, R., Wagner, D. S. and Lozano, G. (1995). Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378, 203-206.
32. Nakano, K. and Vousden, K. H. (2001). PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell 7, 683-694.
33. Niwa, H., Yamamura, K. and Miyazaki, J. (1991). Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108, 193-199.
34. Noda, A., Ning, Y., Venable, S. F., Pereira-Smith, O. M. and Smith, J. R. (1994). Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res. 211, 90-98.
35. 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.
36. Reifenberger, G., Liu, L., Ichimura, K., Schmidt, E. E. and Collins, V. P. (1993). Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 53, 2736-2739.
37. Schuster, K. and Harris, L. C. (2007). Selection for mutations in the cDNAs of transgenic mice upon expression of an embryonic lethal protein. Transgenic Res. 16, 527-530.
38. Sigalas, I., Calvert, A. H., 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.
39. Steinman, H. A., Burstein, E., Lengner, C., Gosselin, J., Pihan, G., Duckett, C. S. and Jones, S. N. (2004). An alternative splice form of Mdm2 induces p53-independent cell growth and tumorigenesis. J. Biol. Chem. 279, 4877-4886.
40. Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C. et al. (2002). p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45-53.
41. Varela, I., Cadinanos, J., Pendas, A. M., Gutierrez-Fernandez, A., Folgueras, A. R., Sanchez, L. M., Zhou, Z., Rodriguez, F. J., Stewart, C. L., Vega, J. A. et al. (2005). Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437, 564-568.
42. Yonish-Rouach, E., Resnitzky, D., Lotem, J., Sachs, L., Kimchi, A. and Oren, M. (1991). Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352, 345-347.
43. Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W. and Vogelstein, B. (2001). PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell 7, 673-682.