Identification of an aberrantly spliced form of HDMX in human tumors: A new mechanism for HDM2 stabilization

Cancer Research

Volumn 65, Issue 21, 2005, Pages 9687-9694

  Giglio, Simona ^a   Mancini, Francesca ^a   Gentiletti, Francesca ^a   Sparaco, Giorgia ^a   Felicioni, Lara ^b   Barassi, Fabio ^b   Martella, Carla ^b   Prodosmo, Andrea ^a   Iacovelli, Stefano ^a   Buttitta, Fiamma ^b   Farsetti, Antonella ^a   Soddu, Silvia ^a   Marchetti, Antonio ^b   Sacchi, Ada ^a   Pontecorvi, Alfredo ^a   Moretti, Fabiola ^a,c  

^a CATHOLIC UNIVERSITY   (Italy)

^b UNIVERSITY OF CHIETI   (Italy)

^c REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; MESSENGER RNA; ONCOPROTEIN; PROTEIN HDMX; PROTEIN HDMX211; PROTEIN INHIBITOR; PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CANCER INHIBITION; CARCINOGENESIS; CELL ASSAY; CELL CYCLE; CELL FUNCTION; CELL PROLIFERATION; CLONOGENESIS; COLONY FORMING CELL; CONTROLLED STUDY; DRUG SENSITIVITY; HUMAN; HUMAN CELL; LUNG CANCER; MOLECULAR CLONING; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN ISOLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; THYROID TUMOR; TRANSCRIPTION REGULATION; TUMOR BIOPSY; TUMOR CELL LINE; WILD TYPE;

ALTERNATIVE SPLICING; ANIMALS; CELL GROWTH PROCESSES; CELL LINE, TUMOR; HUMANS; MICE; NIH 3T3 CELLS; NUCLEAR PROTEINS; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, MESSENGER; THYROID NEOPLASMS; TRANSFECTION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 27544493522     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-05-0450     Document Type: Article

References (43)

1. Lozano G, Montes de Oca Luna R. MDM2 function. Biochim Biophys Acta 1998;1377:55-9.
2. Moll UM, Petrenko O. The MDM2-p53 interaction. Mol Cancer Res 2003;1:1001-8.
3. Alarcon-Vargas D, Ronai Z. p53-Mdm2-the affair that never ends. Carcinogenesis 2002;23:541-7.
4. Momand J, Jung D, Wilczynski S, Niland J. The MDM2 gene amplification database. Nucleic Acids Res 1998;26: 3453-9.
5. Landers JE, Cassel SL, George DL. Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. Cancer Res 1997;57:3562-8.
6. Bueso-Ramos CE, Manshouri T, Haidar MA, et al. Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat 1996;37:179-88.
7. Bueso-Ramos CE, Yang Y, deLeon E, McCown P, Stass SA, Albitar M. The human MDM-2 oncogene is overexpressed in leukemias. Blood 1993;82:2617-23.
8. Capoulade C, Bressac-de Paillerets B, Lefrere I, et al. Overexpression of MDM2, due to enhanced translation, results in inactivation of wild-type p53 in Burkitt's lymphoma cells. Oncogene 1998;16:1603-10.
9. Berberich S, Cole M. The mdm-2 oncogene is translocated and overexpressed in a murine plasmacytoma cell line expressing wild-type p53. Oncogene 1994;9: 1469-72.
10. Trotta R, Vignudelli T, Candini O, et al. BCR/ABL activates mdm2 mRNA translation via the La antigen. Cancer Cell 2003;3:145-60.
11. Evans SC, Viswanathan M, Grier JD, Narayana M, El-Naggar A, Lozano G. An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. Oncogene 2001;20:4041-9.
12. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2002;2:9-15.
13. 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 U S A 1998;95:15608-12.
14. Lundgren K, Montes de Oca Luna R, McNeill YB, et al. Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53. Genes Dev 1997;11:714-25.
15. Shvarts A, Steegenga WT, Riteco N, et al. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 1996;15:5349-57.
16. Sharp DA, Kratowicz SA, Sank MJ, George DL. Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. J Biol Chem 1999;274:38189-96.
17. Shvarts A, Bazuine M, Dekker P, et al. Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. Genomics 1997;43:34-42.
18. Riemenschneider MJ, Buschges R, Wolter M, et al. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res 1999;59:6091-6.
19. Danovi D, Meulmeester E, Pasini D, et al. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 2004;24:5835-43.
20. Ramos YF, Stad R, Attema J, Peltenburg LT, van der Eb AJ, Jochemsen AG. Aberrant expression of HDMX proteins in tumor cells correlates with wild-type p53. Cancer Res 2001;61:1839-42.
21. Rallapalli R, Strachan G, Cho B, Mercer WE, Hall DJ. A novel MDMX transcript expressed in a variety of transformed cell lines encodes a truncated protein with potent p53 repressive activity. J Biol Chem 1999;274:299-308.
22. Gentiletti E, Mancini F, D'Angelo M, et al. MDMX stability is regulated by p53-induced caspase cleavage in NIH3T3 mouse fibroblasts. Oncogene 2002;21:867-77.
23. Moretti F, Farsetti A, Soddu S, et al. p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene 1997;14:729-40.
24. Marchetti A, Barassi F, Martella C, et al. Down-regulation of high in normal-1 (HIN-1) is a frequent event in stage I non-small cell lung cancer and correlates with poor clinical outcome. Clin Cancer Res 2004;10:1338-43.
25. Ghosh M, Huang K, Berberich SJ. Overexpression of Mdm2 and MdmX fusion proteins alters p53 mediated transactivation, ubiquitination, and degradation. Biochemistry 2003;42:2291-9.
26. Freedman DA, Levine AJ. Regulation of the p53 protein by the MDM2 oncoprotein-thirty-eighth G.H.A. Clowes Memorial Award Lecture. Cancer Res 1999;59:1-7.
27. Stad R, Ramos YF, Little N, et al. Hdmx stabilizes Mdm2 and p53. J Biol Chem 2000;275:28039-44.
28. Stad R, Little NA, Xirodimas DP, et al. Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms. EMBO Rep 2001;2:1029-34.
29. Stommel JM, Wahl GM. Accelerated MDM2 autodegradation induced by DNA-damage kinases is required for p53 activation. EMBO J 2004;23:1547-56.
30. Lin J, Chen J, Elenbaas B, Levine AJ. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994;15:1235-46.
31. Jimenez GS, Nister M, Stommel JM, et al. A transactivation-deficient mouse model provides insights into Trp53 regulation and function. Nat Genet 2000;26:37-43.
32. Dornan D, Wertz I, Shimizu H, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004;429:86-92.
33. Leng RP, Lin Y, Ma W, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003;112:779-91.
34. Lain S, Xirodimas DP, Lane DP. Accumulating active p53 in the nucleus by inhibition of nuclear export: a novel strategy to promote the p53 tumor suppressor function. Exp Cell Res 1999;53:315-24.
35. Menendez S, Higgins M, Berkson RG, Edling C, Lane DP, Lain S. Nuclear export inhibitor leptomycin B induces the appearance of novel forms of human Mdm2 protein. Br J Cancer 2003;88:636-43.
36. Gu J, Kawai H, Nie L, et al. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem 2002;277:19251-4.
37. Deb SP. Cell cycle regulatory functions of the human oncoprotein MDM2. Mol Cancer Res 2003;1:1009-16.
38. Ganguli G, Wasylyk B. p53-independent functions of MDM2. Mol Cancer Res 2003;1:1027-35.
39. Brown DR, Thomas CA, Deb SP. The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis. EMBO J 1998;17:2513-25.
40. Marchetti A, Buttitta F, Pellegrini S, et al. mdm2 gene amplification and overexpression in non-small cell lung carcinomas with accumulation of the p53 protein in the absence of p53 gene mutations. Diagn Mol Pathol 1995; 4:93-7.
41. Keleti J, Quezado MM, Abaza MM, Raffeld M, Tsokos M. The MDM2 oncoprotein is overexpressed in rhabdomyosarcoma cell lines and stabilizes wild-type p53 protein. Am J Pathol 1996;149:143-51.
42. Mancini F, Gentiletti F, D'Angelo M, et al. MDM4 (MDMX) overexpression enhances stabilization of stress-induced p53 and promotes apoptosis. J Biol Chem 2004;279:8169-80.
43. Steinman HA, Sluss HK, Sands AT, Pihan G, Jones SN. Absence of p21 partially rescues Mdm4 loss and uncovers an antiproliferative effect of Mdm4 on cell growth. Oncogene 2004;23:303-6.