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 Journal

Volumn 17, Issue 2, 1998, Pages 554-564

  Roth, Judith ^a,b   Dobbelstein, Matthias ^a,b   Freedman, Deborah A ^a   Shenk, Thomas ^a   Levine, Arnold J ^a  

^a PRINCETON UNIVERSITY   (United States)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

hdm2; HIV; Nucleo cytoplasmic transport; Oncogene; p53

Indexed keywords

HYBRID PROTEIN; ONCOPROTEIN; PROTEIN P53; REV PROTEIN;

ARTICLE; CELL GROWTH; CELL NUCLEUS; CONTROLLED STUDY; CYTOPLASM; GENE MUTATION; HELA CELL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; LENTIVIRINAE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; TRANSCRIPTION INITIATION; TUMOR SUPPRESSOR GENE;

AMINO ACID SEQUENCE; BIOLOGICAL TRANSPORT; CARRIER PROTEINS; CELL NUCLEUS; CYTOPLASM; GENE PRODUCTS, REV; HELA CELLS; HUMANS; MOLECULAR SEQUENCE DATA; NUCLEAR PROTEINS; PROTEIN SORTING SIGNALS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; TRANS-ACTIVATION (GENETICS); TUMOR SUPPRESSOR PROTEIN P53;

HUMAN IMMUNODEFICIENCY VIRUS; LENTIVIRUS;

EID: 0032518917     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/17.2.554     Document Type: Article

References (91)

1. Babiss, L.E., Ginsberg, H.S. and Darnell, J.E., Jr (1985) Adenovirus E1B proteins are required for accumulation of late viral mRNA and for effects on cellular mRNA translation and transport. Mol. Cell. Biol., 5, 2552-2558.
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. Berberich, S. and Cole, M. (1994) The mdm-2 oncogene is translocated and overexpressed in a murine plasmacytoma cell line expressing wild-type p53. Oncogene, 9, 1469-1472.
4. Bevec, D. et al. (1996) Inhibition of HIV-1 replication in lymphocytes by mutants of the Rev cofactor eIF-5A. Science, 271, 1858-1860.
5. Bogerd, H.P., Fridell, R.A., Madore, S. and Cullen, B.R. (1995) Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins. Cell, 82, 485-494.
6. Bogerd, H.P., Fridell, R.A., Benson, R.E., Hua, J. and Cullen, B.R. (1996) Protein sequence requirements for function of the human T-cell leukemia virus type 1 rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Mol. Cell. Biol., 16, 4207-4214.
7. Boulikas, T. (1993) Nuclear localization signals (NLS). Crit. Rev. Eukaryot. Gene Expr., 3, 193-227.
8. Bueso-Ramos, C.E., Yang, Y., deLeon, E., McCown, P., Stass, S.A. and Albitar, M. (1993) The human MDM-2 oncogene is overexpressed in leukemias. Blood, 82, 2617-2623.
9. Chen, J., Lin, J. and Levine, A.J. (1995) Regulation of transcription functions of the p53 tumor suppressor by the mdm-2 oncogene. Mol. Med., 1, 142-152.
10. 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.
11. Chen, J., Marechal, V. and Levine, A.J. (1993) Mapping of the p53 and mdm-2 interaction domains. Mol. Cell. Biol., 13, 4107-4114.
12. Cordon-Cardo, C. et al. (1994) Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res., 54, 794-799.
13. Dietrich, C. Bartsch, T., Schanz, F., Oesch, F. and Wieser, R.J. (1996) p53-dependent cell cycle arrest induced by N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal in platelet-derived growth factor-stimulated human fibroblasts. Proc. Natl Acad. Sci. USA, 93, 10815-10819.
14. Dobbelstein, M. and Shenk, T. (1995) In vitro selection of RNA ligands for the ribosomal L22 protein associated with Epstein-Barr virus-expressed RNA by using randomized and cDNA-derived RNA libraries. J. Virol., 69, 8027-8034.
15. Dobbelstein, M. and Shenk, T. (1996) Protection against apoptosis by the vaccinia virus SPI-2 (B13R) gene product. J. Virol., 70, 6479-6485.
16. Dobbelstein, M., Arthur, A.K., Dehde, S., van Zee, K., Dickmanns, A. and Fanning, E. (1992) Intracistronic complementation reveals a new function of SV40 T antigen that co-operates with Rb and p53 binding to stimulate DNA synthesis in quiescent cells. Oncogene, 7, 837-847.
17. Dobbelstein, M., Roth, J., Kimberly, W.T., Levine, A.J. and Shenk, T. (1997) Nuclear export of the E1B 55-kDa and E4 34-kDa adenoviral oncoproteins mediated by a rev-like signal sequence. EMBO J., 16, 4276-4284.
18. Dobner, T., Horikoshi, N., Rubenwolf, S. and Shenk, T. (1996) Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor. Science, 272, 1470-1473.
19. Elenbaas, B., Dobbelstein, M., Roth, J., Shenk, T. and Levine, A.J. (1996) The MDM2 oncoprotein binds specifically to RNA through its RING finger domain. Mol. Med., 2, 439-451.
20. Fiddler, T.A., Smith, L., Tapscott, S.J. and Thayer, M.J. (1996) Amplification of MDM2 inhibits MyoD-mediated myogenesis. Mol. Cell. Biol., 16, 5048-5057.
21. Finlay, C.A. (1993) The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol. Cell. Biol., 13, 301-306.
22. Fischer, U., Huber, J., Boelens, W.C., Mattaj, I.W. and Luhrmann, R. (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell, 82, 475-483.
23. Freedman, D.A., Epstein, C.B., Roth, J.C. and Levine, A.J. (1997) A genetic approach to mapping the p53 binding site in the MDM2 protein. Mol. Med., 3, 248-259.
24. Fridell, R.A., Fischer, U., Luhrmann, R., Meyer, B.E., Meinkoth, J.L., Malim, M.H. and Cullen, B.R. (1996) Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Proc. Natl Acad. Sci. USA, 93, 2936-2940.
25. Fritz, C.C. Zapp, M.L. and Green, M.R. (1995) A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature, 376, 530-533.
26. Gannon, J.V. and Lane, D.P. (1991) Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport. Nature, 349, 802-806.
27. Gerace, L. (1995) Nuclear export signals and the fast track to the cytoplasm. Cell, 82, 341-344.
28. Goodrum, F.D., Shenk, T. and Ornelles, D.A. (1996) Adenovirus early region 4 34-kilodalton protein directs the nuclear localization of the early region 1B 55-kilodalton protein in primate cells. J. Virol., 70, 6323-6335.
29. Gorlich, D. and Mattaj, I.W. (1996) Nucleocytoplasmic transport. Science, 271, 1513-1518.
30. Gottlieb, T.M. and Jackson, S.P. (1993) The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell, 72, 131-142.
31. Guddat, U., Bakken, A.H. and Pieler, T. (1990) Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in Xenopus oocytes. Cell, 60, 619-28.
32. 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.
33. Halbert, D.N., Cutt, J.R. and Shenk, T. (1985) Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J. Virol., 56, 250-257.
34. Haupt, Y., Maya, R., Kazaz, A. and Oren, M. (1997) Mdm2 promotes the rapid degradation of p53. Nature, 387, 296-299.
35. Hope, T.J., Bond, B.L., McDonald, D., Klein, N.P. and Parslow, T.G. (1991) Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif. J. Virol., 65, 6001-6007.
36. Izaurralde, E. and Mattaj, I.W. (1995) RNA export. Cell, 81, 153-159.
37. Jarmolowski, A., Boelens, W.C. Izaurralde, E. and Mattaj, I.W. (1994) Nuclear export of different classes of RNA is mediated by specific factors. J. Cell. Biol., 124, 627-635.
38. Jentsch, S. and Schlenker, S. (1995) Selective protein degradation: a journey's end within the proteasome. Cell, 82, 881-884.
39. 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.
40. Kao, C.C. Yew, P.R. and Berk, A.J. (1990) Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology, 179, 806-814.
41. Katahira, J., Ishizaki, T., Sakai, H., Adachi, A., Yamamoto, K. and Shida, H. (1995) Effects of translation initiation factor eIF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunodeficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding. J. Virol., 69, 3125-3133.
42. Knippschild, U., Oren, M. and Deppert, W. (1996) Abrogation of wild-type p53 mediated growth-inhibition by nuclear exclusion. Oncogene, 12, 1755-1765.
43. Kubbutat, M.H., Jones, S.N. and Vousden, K.H. (1997) Regulation of p53 stability by Mdm2. Nature, 387, 299-303.
44. Kussie, P.H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A.J. and Pavletich, N.P. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science, 274, 948-953.
45. 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.
46. Landers, J.E., Haines, D.S., Strauss, J.F.R. and George, D.L. (1994) Enhanced translation: a novel mechanism of mdm2 oncogene overexpression identified in human tumor cells. Oncogene, 9, 2745-2750.
47. Leach, F.S. et al. (1993) p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res., 53, 2231-2234.
48. Liang, S., Hitomi, M. and Tartakoff, A.M. (1995) Adenoviral E1B-55kDa protein inhibits yeast mRNA export and perturbs nuclear structure. Proc. Natl Acad. Sci. USA, 92, 7372-7375.
49. Lin, J., Chen, J., Elenbaas, B. and Levine, A.J. (1994) Several Hydrophobic amino acids in the p53 ammo-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev., 8, 1235-1246.
50. Marechal, V., Elenbaas, B., Piette, J., Nicolas, J.C. and Levine, A.J. (1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell. Biol., 14, 7414-7420.
51. Martin, K., Trouche, D., Hagemeier, C., Sorensen, T.S., La Thangue, N.B. and Kouzarides, T. (1995) Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature, 375, 691-694.
52. McMasters, K.M., Montes de Oca Luna, R.M., Pena, J.R. and Lozano, G. (1996) mdm2 deletion does not alter growth characteristics of p53-deficient embryo fibroblasts. Oncogene, 13, 1731-1736.
53. Meyer, B.E., Meinkoth, J.L. and Malim, M.H. (1996) Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals. J. Virol., 70, 2350-2359.
54. Michael, W.M. and Dreyfuss, G. (1996) Distinct domains in ribosomal protein L5 mediate 5S rRNA binding and nucleolar localization. J. Biol. Chem., 217, 11571-11574.
55. Michael, W.M., Choi, M. and Dreyfuss, G. (1995) A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway. Cell, 83, 415-422.
56. Mittnacht, S. and Weinberg, R.A. (1991) G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell, 65, 381-393.
57. Moll, U.M., Riou, G. and Levine, A.J. (1992) Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc. Natl Acad. Sci. USA, 89, 7262-7266.
58. Moll, U.M., LaQuaglia, M., Benard, J. and Riou, G. (1995) Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors. Proc. Natl Acad. Sci. USA, 92, 4407-4411.
59. Momand, J. and Zambetti, G.P. (1996) Analysis of the proportion of p53 bound to mdm-2 in cells with defined growth characteristics. Oncogene, 12, 2279-2289.
60. 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.
61. 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.
62. Moore, M.S. (1996) Protein translocation: nuclear export - out of the dark. Curr. Biol., 6, 137-140.
63. Moore, M., Horikoshi, N. and Shenk, T. (1996) Oncogenic potential of the adenovirus E4orf6 protein. Proc. Natl Acad. Sci. USA, 93, 11295-11301.
64. Mosner, J., Mummenbrauer, T., Bauer, C., Sczakiel, G., Grosse, F. and Deppert, W. (1995) Negative feedback regulation of wild-type p53 biosynthesis. EMBO J., 14, 4442-4449.
65. Murphy, R. and Wente, S.R. (1996) An RNA-export mediator with an essential nuclear export signal. Nature, 383, 357-360.
66. 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, 80-3.
67. Oliner, J.D., Pietenpol, J.A., Thiagalingam, S., Gyuris, J., Kinzler, K.W. and Vogelstein, B. (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature, 362, 857-860.
68. Olson, D.C., Marechal, V., Momand, J., Chen, J., Romocki, C. and Levine, A.J. (1993) Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene, 8, 2353-2360.
69. Palmer, A., Rivett, A.J., Thomson, S., Hendil, K.B., Butcher, G.W., Fuertes, G. and Knecht, E. (1996) Subpopulations of proteasomes in rat liver nuclei, microsomes and cytosol. Biochem. J., 316, 401-407.
70. Palmeri, D. and Malim, M.H. (1996) The human T-cell leukemia virus type 1 posttranscriptional trans-activator Rex contains a nuclear export signal. J. Virol., 70, 6442-6445.
71. Pilder, S., Moore, M., Logan, J. and Shenk, T. (1986) The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs. Mol. Cell. Biol., 6, 470-476.
72. Pinol-Roma, S. and Dreyfuss, G. (1992) Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature, 355, 730-732.
73. Plemper, R.K., Bohmler, S., Bordallo, J., Sommer, T. and Wolf, D.H. (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature, 388, 891-893.
74. 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.
75. Rudt, F. and Pieler, T. (1996) Cytoplasmic retention and nuclear import of 5S ribosomal RNA containing RNPs. EMBO J., 15, 1383-1391.
76. Sarnow, P., Ho, Y.S., Williams, J. and Levine, A.J. (1982) Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kDa cellular protein in transformed cells. Cell, 28, 387-394.
77. Sarnow, P., Hearing, P., Anderson, C.W., Halbert, D.N., Shenk, T. and Levine, A.J. (1984) Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells. J. Virol., 49, 692-700.
78. Shaulsky, G., Ben-Ze'ev, A. and Rotter, V. (1990) Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene, 5, 1707-1711.
79. Shaulsky, G., Goldfinger, N., Tosky, M.S., Levine, A.J. and Rotter, V. (1991) Nuclear localization is essential for the activity of p53 protein. Oncogene, 6, 2055-2065.
80. Shenk, T. (1996) In Fields, B.N., Knipe D.M. and Howley, P.M. (eds), Adenoviridae. The Viruses and Their Replication. Lippincott-Raven, Philadelphia, PA, pp. 979-1016.
81. Simos, G. and Hurt, E.C. (1995) Nucleocytoplasmic transport: factors and mechanisms. FEBS Lett., 369, 107-112.
82. Stutz, F., Neville, M. and Rosbash, M. (1995) Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Cell, 82, 495-506.
83. Walker, K.K. and Levine, A.J. (1996) Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc. Natl Acad. Sci. USA, 93, 15335-15340.
84. Wen, W., Meinkoth, J.L., Tsien, R.Y. and Taylor, S.S. (1995) Identification of a signal for rapid export of proteins from the nucleus. Cell, 82, 463-473.
85. Wojcik, C., Paweletz, N. and Schroeter, D. (1995) Localization of proteasomal antigens during different phases of the cell cycle in HeLa cells. Eur. J. Cell. Biol., 68, 191-198.
86. Wojcik, C., Schroeter, D., Wilk, S., Lamprecht, J. and Paweletz, N. (1996) Ubiquitin-mediated proteolysis centers in HeLa cells: indication from studies of an iphibitor of the chymotrypsin-like activity of the proteasome. Eur. J. Cell. Biol., 71, 311-318.
87. Wu, X., Bayle, J.H., Olson, D. and Levine, A.J. (1993) The p53-mdm-2 autoregulatory feedback loop. Genes Dev., 7, 1126-1132.
88. Xiao, Z.X., Chen, J., Levine, A.J., Modjtahedi, N., Xing, J., Sellers, W.R. and Livingston, D.M. (1995) Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature, 375, 694-698.
89. Yew, P.R. and Berk, A.J. (1992) Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature, 357, 82-85.
90. 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.
91. Zhu, H., Shen, Y. and Shenk, T. (1995) Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J. Virol., 69, 7960-7970.