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Cell Growth and Development

Loss of IκBα-Mediated Control over Nuclear Import and DNA Binding Enables Oncogenic Activation of c-Rel

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Pages 5445-5456 | Received 13 Mar 1998, Accepted 10 Jun 1998, Published online: 28 Mar 2023

REFERENCES

  • Alkalay, I., A. Yaron, A. Hatzubai, A. Orian, A. Ciechanover, and Y. Ben-Neriah 1995. Stimulation-dependent IκBα phosphorylation marks the NF-κB inhibitor for degradation via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 92: 10599–10603.
  • Arenzana-Seisdedos, F., J. Thompson, M. S. Rodriguez, F. Bachelerie, D. Thomas, and R. T. Hay 1995. Inducible nuclear expression of newly synthesized IκBα negatively regulates DNA-binding and transcriptional activities of NF-κB. Mol. Cell. Biol. 15: 2689–2696.
  • Arenzana-Seisdedos, F., P. Turpin, M. Rodriguez, D. Thomas, R. T. Hay, J. L. Virelizier, and C. Dargemont 1997. Nuclear localization of IκBα promotes active transport of NF-κB from the nucleus to the cytoplasm. J. Cell Sci. 110: 369–378.
  • Baldwin, A. S.Jr. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14: 649–683.
  • Beg, A. A., S. M. Ruben, R. I. Scheinman, S. Haskill, C. A. Rosen, Baldwin A. S., Jr. 1992. IκB interacts with the nuclear localization sequences of the subunits of NF-κB: a mechanism for cytoplasmic retention. Genes Dev. 6: 1899–1913.
  • Brockman, J. A., D. C. Scherer, T. A. McKinsey, S. M. Hall, X. Qi, W. Y. Lee, and D. W. Ballard 1995. Coupling of a signal response domain in IκBα to multiple pathways for NF-κB activation. Mol. Cell. Biol. 15: 2809–2816.
  • Capobianco, A. J., D. L. Simmons, and T. D. Gilmore 1990. Cloning and characterization of a chicken c-Rel cDNA: unlike p59v-rel, p68c-rel is a cytoplasmic protein in chicken embryo fibroblasts. Oncogene 5: 257–266.
  • Carrasco, D., P. Perez, A. Lewin, and R. Bravo 1997. IκBα overexpression delays tumor formation in v-rel transgenic mice. J. Exp. Med. 186: 279–288.
  • Carrasco, D., C. A. Rizzo, K. Dorfman, and R. Bravo 1996. The v-rel oncogene promotes malignant T-cell leukemia/lymphoma in transgenic mice. EMBO J. 15: 3640–3650.
  • Chang, C. C., J. Zhang, L. Lombardi, A. Neri, and R. Dalla-Favera 1995. Rearranged NFKB-2 genes in lymphoid neoplasms code for constitutively active nuclear transactivators. Mol. Cell. Biol. 15: 5180–5187.
  • Chen, Z., J. Hagler, V. J. Palombella, F. Melandri, D. Scherer, D. Ballard, and T. Maniatis 1995. Signal-induced site-specific phosphorylation targets IκBα to the ubiquitin-proteasome pathway. Genes Dev. 9: 1586–1597.
  • Cressman, D. E., and R. Taub 1993. IκBα can localize in the nucleus but shows no direct transactivation potential. Oncogene 8: 2567–2573.
  • Davis, N., W. Bargmann, M. Y. Lim, Bose H., Jr. 1990. Avian reticuloendotheliosis virus-transformed lymphoid cells contain multiple pp59v-rel complexes. J. Virol. 64: 584–591.
  • Davis, N., S. Ghosh, D. L. Simmons, P. Tempst, H. C. Liou, D. Baltimore, Bose H. R., Jr. 1991. rel-associated pp40: an inhibitor of the rel family of transcription factors. Science 253: 1268–1271.
  • DiDonato, J. A., M. Hayakawa, D. M. Rothwarf, E. Zandi, and M. Karin 1997. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature (London) 388: 548–554.
  • Diehl, J. A., T. A. McKinsey, and M. Hannink 1993. Differential pp40IκB-β inhibition of DNA binding by rel proteins. Mol. Cell. Biol. 13: 1769–1778.
  • Diehl, J. A., W. Tong, G. Sun, and M. Hannink 1995. TNF-α-dependent activation of a RelA homodimer in astrocytes: increased phosphorylation of RelA and MAD-3 precede activation of RelA. J. Biol. Chem. 270: 2703–2707.
  • Dougherty, J. P., and H. M. Temin 1986. High mutation rate of a spleen necrosis virus-based retrovirus vector. Mol. Cell. Biol. 6: 4387–4395.
  • Finco, T. S., J. K. Westwick, J. L. Norris, A. A. Beg, C. J. Der, Baldwin A. S., Jr. 1997. Oncogenic Ha-Ras-induced signaling activates NF-κB transcriptional activity, which is required for cellular transformation. J. Biol. Chem. 272: 24113–24116.
  • Fischer, U., J. Huber, W. C. Boelens, I. W. Mattaj, and R. Luhrmann 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.
  • Fornerod, M., M. Ohno, M. Yoshida, and I. W. Mattaj 1997. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90: 1051–1060.
  • Fukuda, M., S. Asano, T. Nakamura, M. Adachi, M. Yoshida, M. Yanagida, and E. Nishida 1997. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature (London) 390: 308–311.
  • Ganchi, P. A., S. C. Sun, W. C. Greene, and D. W. Ballard 1992. IκB/MAD-3 masks the nuclear localization signal of NF-κB p65 and requires the transactivation domain to inhibit NF-κB p65 DNA binding. Mol. Biol. Cell 3: 1339–1352.
  • Ghattas, I. R., J. R. Sanes, and J. E. Majors 1991. The encephalomyocarditis virus internal ribosome entry site allows efficient coexpression of two genes from a recombinant provirus in cultured cells and in embryos. Mol. Cell. Biol. 11: 5848–5859.
  • Gilmore, T. D., and H. M. Temin 1986. Different localization of the product of the v-rel oncogene in chicken fibroblasts and spleen cells correlates with transformation by REV-T. Cell 44: 791–800.
  • Gilmore, T. D., M. Koedood, K. A. Piffat, and D. W. White 1996. Rel/NF-κB/IκB proteins and cancer. Oncogene 13: 1367–1378.
  • Görlich, D., and I. W. Mattaj 1996. Nucleocytoplasmic transport. Science 271: 1513–1518.
  • Hrdlickova, R., J. Nehyba, and E. H. Humphries 1994. In vivo evolution of c-rel oncogenic potential. J. Virol. 68: 2371–2382.
  • Hrdlickova, R., J. Nehyba, Bose H. R., Jr. 1995. Mutations in the DNA-binding and dimerization domains of v-Rel are responsible for altered κB DNA-binding complexes in transformed cells. J. Virol. 69: 3369–3380.
  • Hrdlickova, R., J. Nehyba, A. Roy, E. H. Humphries, Bose H. R., Jr. 1995. The relocalization of v-Rel from the nucleus to the cytoplasm coincides with induction of expression of Ikba and nfkb1 and stabilization of IκB-α. J. Virol. 69: 403–413.
  • Ito, C. Y., A. G. Kazantsev, Baldwin A. S., Jr. 1994. Three NF-κB sites in the IκB-α promoter are required for induction of gene expression by TNF-α. Nucleic Acids Res. 22: 3787–3792.
  • Le Bail, O., R. Schmidt-Ullrich, and A. Israel 1993. Promoter analysis of the gene encoding the I κBα/MAD-3 inhibitor of NF-κB: positive regulation by members of the Rel/NF-κB family. EMBO J. 12: 5043–5049.
  • Mayo, M. W., C.-Y. Wang, P. C. Cogswell, K. S. Rogers-Graham, S. W. Lowe, C. J. Der, Baldwin A. S., Jr. 1998. Requirement of NF-κB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278: 1812–1815.
  • Mercurio, F., H. Zhu, B. W. Murray, A. Shevchenko, B. L. Bennett, J. Li, D. B. Young, M. Barbosa, M. Mann, A. Manning, and A. Rao 1997. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278: 860–866.
  • Michael, W. M., M. Choi, and G. Dreyfuss 1995. A nuclear export signal in hnRNP A1: a signal-mediated temperature-dependent nuclear protein export pathway. Cell 83: 415–422.
  • Morin, P. J., and T. D. Gilmore 1992. The C-terminus of the NF-κB p50 precursor and an IκB isoform contain transcription activation domains. Nucleic Acids Res. 20: 2453–2458.
  • Nehyba, J., R. Hrdlickova, Bose H. R., Jr. 1997. Differences in κB DNA-binding properties of v-Rel and c-Rel are the result of oncogenic mutations in three distinct functional regions of the Rel protein. Oncogene 14: 2881–2897.
  • Nigg, E. A. 1997. Nucleocytoplasmic transport: signals, mechanisms and regulation. Nature (London) 386: 779–787.
  • Nishi, K., M. Yoshida, D. Fujiwara, M. Nishikawa, S. Horinouchi, and T. Beppu 1994. Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J. Biol. Chem. 269: 6320–6324.
  • Ossareh-Nazari, B., F. Bachelerie, and C. Dargemont 1997. Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science 278: 141–144.
  • Regnier, C. H., H. Y. Song, X. Gao, D. V. Goeddel, Z. Cao, and M. Rothe 1997. Identification and characterization of an IκB kinase. Cell 90: 373–383.
  • Richardson, P. M., and T. D. Gilmore 1991. v-Rel is an inactive member of the Rel family of transcriptional activating proteins. J. Virol. 65: 3122–3130.
  • Rottjakob, E. M., S. Sachdev, C. A. Leanna, T. A. McKinsey, and M. Hannink 1996. PEST-dependent cytoplasmic retention of v-Rel by IκB-α: evidence that IκB-α regulates cellular localization of c-Rel and v-Rel by distinct mechanisms. J. Virol. 70: 3176–3188.
  • Sachdev, S., E. M. Rottjakob, J. A. Diehl, and M. Hannink 1995. IκB-α-mediated inhibition of nuclear transport and DNA-binding by Rel proteins are separable functions: phosphorylation of C-terminal serine residues of IκB-α is specifically required for inhibition of DNA-binding. Oncogene 11: 811–823.
  • Sachdev, S., J. A. Diehl, T. A. McKinsey, A. Hans, and M. Hannink 1997. A threshold nuclear level of the v-Rel oncoprotein is required for transformation of avian lymphocytes. Oncogene 14: 2585–2594.
  • Sachdev, S., A. Hoffmann, and M. Hannink 1998. Nuclear localization of IκBα is mediated by the second ankyrin repeat: the IκBα ankyrin repeats define a novel class of cis-acting nuclear import sequences. Mol. Cell. Biol. 18: 2524–2534.
  • Sachdev, S., and M. Hannink. Unpublished data.
  • Sambrook, J., E. F. Fritsch, and T. Maniatis 1989. Molecular cloning: a laboratory manual2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
  • Schatzle, J. D., J. Kralova, Bose H. R., Jr. 1995. Avian IκBα is transcriptionally induced by c-Rel and v-Rel with different kinetics. J. Virol. 69: 5383–5390.
  • Scherer, D. C., J. A. Brockman, Z. Chen, T. Maniatis, and D. W. Ballard 1995. Signal-induced degradation of IκBα requires site-specific ubiquitination. Proc. Natl. Acad. Sci. USA 92: 11259–11263.
  • Simek, S. L., R. M. Stephens, and N. R. Rice 1986. Localization of the v-rel protein in reticuloendotheliosis virus strain T-transformed lymphoid cells. J. Virol. 59: 120–126.
  • Stade, K., C. S. Ford, C. Guthrie, and K. Weis 1997. Exportin 1 (Crm1p) is an essential nuclear export factor. Cell 90: 1041–1050.
  • Sun, S. C., P. A. Ganchi, D. W. Ballard, and W. C. Greene 1993. NF-κB controls expression of inhibitor κBα: evidence for an inducible autoregulatory pathway. Science 259: 1912–1915.
  • Sylla, B. S., and H. M. Temin 1986. Activation of oncogenicity of the c-rel proto-oncogene. Mol. Cell. Biol. 6: 4709–4716.
  • Traenckner, E. B., H. L. Pahl, T. Henkel, K. N. Schmidt, S. Wilk, and P. A. Baeuerle 1995. Phosphorylation of human IκB-α on serines 32 and 36 controls IκB-α proteolysis and NF-κB activation in response to diverse stimuli. EMBO J. 14: 2876–2883.
  • Tran, K., M. Merika, and D. Thanos 1997. Distinct functional properties of IκBα and IκBβ. Mol. Cell. Biol. 17: 5386–5399.
  • Wen, W., J. L. Meinkoth, R. Y. Tsien, and S. S. Taylor 1995. Identification of a signal for rapid export of proteins from the nucleus. Cell 82: 463–473.
  • Wilhelmsen, K. C., K. Eggleton, and H. M. Temin 1984. Nucleic acid sequences of the oncogene v-rel in reticuloendotheliosis virus strains T and its cellular homolog, the proto-oncogene c-rel. J. Virol. 52: 172–182.
  • Woronicz, J. D., X. Gao, Z. Cao, M. Rothe, and D. V. Goeddel 1997. IκB kinase-β: NF-κB activation and complex formation with IκB kinase-α and NIK. Science 278: 866–869.
  • Yaron, A., H. Gonen, I. Alkalay, A. Hatzubai, S. Jung, S. Beyth, F. Mercurio, A. M. Manning, A. Ciechanover, and Y. Ben-Neriah 1997. Inhibition of NF-κB cellular function via specific targeting of the IκB-ubiquitin ligase. EMBO J. 16: 6486–6494.
  • Zabel, U., T. Henkel, M. S. Silva, and P. A. Baeuerle 1993. Nuclear uptake control of NF-κB by MAD-3, an IκB protein present in the nucleus. EMBO J. 12: 201–211.
  • Zandi, E., D. M. Rothwarf, M. Delhase, M. Hayakawa, and M. Karin 1997. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91: 243–252.

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