Mutations in the v-Rel Transactivation Domain Indicate Altered Phosphorylation and Identify a Subset of NF-κB-Regulated Cell Death Inhibitors Important for v-Rel Transforming Activity

REFERENCES

• Abbadie, C., N. Kabrun, F. Bouali, J. Smardova, D. Stéhelin, B. Vandenbunder, and P. J. Enrietto. 1993. High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro. Cell 75: 899–912.
   PubMed Web of Science ®Google Scholar
• Arlt, A., O. Grobe, A. Sieke, M. L. Kruse, U. R. Folsch, W. E. Schmidt, and H. Schafer. 2001. Expression of the NF-κB target gene IEX-1 (p22/PRG1) does not prevent cell death but instead triggers apoptosis in HeLa cells. Oncogene 20: 69–76.
   PubMed Web of Science ®Google Scholar
• Barkett, M., and T. D. Gilmore. 1999. Control of apoptosis by Rel/NF-κB transcription factors. Oncogene 18: 6910–6924.
   PubMed Web of Science ®Google Scholar
• Beg, A. A., and D. Baltimore. 1996. An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274: 782–784.
   PubMed Web of Science ®Google Scholar
• Boyle, W., P. van der Greer, and T. Hunter. 1991. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 201: 110–149.
   PubMed Web of Science ®Google Scholar
• Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254.
   PubMed Web of Science ®Google Scholar
• Catz, S. D., and J. L. Johnson. 2001. Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer. Oncogene 20: 7342–7351.
   PubMed Web of Science ®Google Scholar
• Chen, C., F. Agnés, and C. Gélinas. 1999. Mapping of a serine-rich domain essential for the transcriptional, antiapoptotic, and transforming activities of the v-Rel oncoprotein. Mol. Cell. Biol. 19: 307–316.
   PubMedGoogle Scholar
• Chen, C., F. Agnés, and C. Gélinas. 2001. Mapping of a serine-rich domain essential for the transcriptional, antiapoptotic, and transforming activities of the v-Rel oncoprotein. Mol. Cell. Biol. 21: 7115. (Author's correction.)
   Google Scholar
• Chen, C., L. C. Edelstein, and C. Gélinas. 2000. The Rel/NF-κB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol. Cell. Biol. 20: 2687–2695.
   PubMed Web of Science ®Google Scholar
• Chen, F., L. M. Demers, V. Vallyathan, Y. Lu, V. Castranova, and X. Shi. 1999. Involvement of 5′-flanking κB-like sites within bcl-x gene in silica-induced Bcl-x expression. J. Biol. Chem. 274: 35591–35595.
   PubMed Web of Science ®Google Scholar
• Chen, F. E., D. B. Huang, Y. Q. Chen, and G. Ghosh. 1998. Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature 391: 410–413.
   PubMed Web of Science ®Google Scholar
• Chen, L., W. Fischle, E. Verdin, and W. C. Greene. 2001. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293: 1653–1657.
   PubMed Web of Science ®Google Scholar
• Chen, Y. Q., S. Ghosh, and G. Ghosh. 1998. A novel DNA recognition mode by the NF-κB p65 homodimer. Nat. Struct. Biol. 5: 67–73.
   PubMedGoogle Scholar
• Cheng, Q., H. H. Lee, Y. Li, T. P. Parks, and G. Cheng. 2000. Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition. Oncogene 19: 4936–4940.
   PubMed Web of Science ®Google Scholar
• Chu, Z. L., T. A. McKinsey, L. Liu, J. J. Gentry, M. H. Malim, and D. W. Ballard. 1997. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control. Proc. Natl. Acad. Sci. USA 94: 10057–10062.
   PubMed Web of Science ®Google Scholar
• Cramer, P., C. J. Larson, G. L. Verdine, and C. W. Muller. 1997. Structure of the human NF-κB p52 homodimer-DNA complex at 2.1 Å resolution. EMBO J. 16: 7078–7090.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Dougherty, J. P., R. Wisniewski, S. Yang, B. W. Rhode, and H. M. Temin. 1989. New retrovirus helper cells with almost no nucleotide sequence homology to retrovirus vectors. J. Virol. 63: 3209–3212.
   PubMed Web of Science ®Google Scholar
• Finco, T. S., J. K. Westwick, J. L. Norris, A. A. Beg, C. J. Der, and A. S. Baldwin. 1997. Oncogenic Ha-Ras-induced signaling activates NF-κB transcriptional activity, which is required for cellular transformation. J. Biol. Chem. 272: 24113–24116.
   PubMed Web of Science ®Google Scholar
• Fujii, M., T. Minamino, M. Nomura, K.-I. Miyamoto, J. Tanaka, and M. Seiki. 1996. Selective activation of the proto-oncogene c-jun promoter by the transforming protein v-Rel. Oncogene 12: 2193–2202.
   PubMedGoogle Scholar
• Furia, B., L. Deng, K. Wu, S. Baylor, K. Kehn, H. Li, R. Donnelly, T. Coleman, and F. Kashanchi. 2002. Enhancement of nuclear factor-κ B acetylation by coactivator p300 and HIV-1 Tat proteins. J. Biol. Chem. 277: 4973–4980.
   PubMed Web of Science ®Google Scholar
• Ghosh, G., G. Van Duyne, S. Ghosh, and P. B. Sigler. 1995. Structure of NF-κB p50 homodimer bound to a κB site. Nature 373: 303–310.
   PubMed Web of Science ®Google Scholar
• Gilmore, T. D., C. Cormier, J. Jean-Jacques, and M. E. Gapuzan. 2001. Malignant transformation of primary chicken spleen cells by human transcription factor c-Rel. Oncogene 20: 7098–7103.
   PubMedGoogle Scholar
• Grumont, R. J., I. J. Rourke, and S. Gerondakis. 1999. Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. Genes Dev. 13: 400–411.
   PubMed Web of Science ®Google Scholar
• Hettmann, T., J. DiDonato, M. Karin, and J. M. Leiden. 1999. An essential role for nuclear factor κB in promoting double positive thymocyte apoptosis. J. Exp Med 189: 145–158.
   PubMed Web of Science ®Google Scholar
• Hinz, M., D. Krappmann, A. Eichten, A. Heder, C. Scheidereit, and M. Strauss. 1999. NF-κB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol. Cell. Biol. 19: 2690–2698.
   PubMed Web of Science ®Google Scholar
• Hrdlickova, R., J. Nehyba, and H. R. Bose, Jr. 2001. Interferon regulatory factor 4 contributes to transformation of v-Rel-expressing fibroblasts. Mol. Cell. Biol. 21: 6369–6386.
   PubMedGoogle Scholar
• Huang, D. B., Y. Q. Chen, M. Ruetsche, C. B. Phelps, and G. Ghosh. 2001. X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2. Structure 9: 669–678.
   PubMedGoogle Scholar
• Kralova, J., A. S. Liss, W. Bargmann, and H. R. Bose, Jr. 1998. AP-1 factors play an important role in transformation induced by the v-rel oncogene. Mol. Cell. Biol. 18: 2997–3009.
   PubMedGoogle Scholar
• Krikos, A., C. D. Laherty, and V. M. Dixit. 1992. Transcriptional activation of the tumor necrosis factor a-inducible zinc finger protein, A20, is mediated by κB elements. J. Biol. Chem. 267: 17971–17976.
   PubMed Web of Science ®Google Scholar
• Kumar, S., A. B. Rabson, and C. Gélinas. 1992. The RxxRxRxxC motif conserved in all Rel/κB proteins is essential for the DNA-binding activity and redox regulation of the v-Rel oncoprotein. Mol. Cell. Biol. 12: 3094–3106.
   PubMed Web of Science ®Google Scholar
• Kurland, J. F., R. Kodym, M. D. Story, K. B. Spurgers, T. J. McDonnell, and R. E. Meyn. 2001. NF-κB1 (p50) homodimers contribute to transcription of the bcl-2 oncogene. J. Biol. Chem. 276: 45380–45386.
   PubMedGoogle Scholar
• Laherty, C. D., N. D. Perkins, and V. M. Dixit. 1993. Human T cell leukemia virus type I Tax and phorbol 12-myristate 13-acetate induce expression of the A20 zinc finger protein by distinct mechanisms involving nuclear factor κB. J. Biol. Chem. 268: 5032–5039.
   PubMedGoogle Scholar
• Lee, H. H., H. Dadgostar, Q. Cheng, J. Shu, and G. Cheng. 1999. NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proc. Natl. Acad. Sci. USA 96: 9136–9141.
   PubMed Web of Science ®Google Scholar
• Liu, J., M. Sodeoka, W. Lane, and G. L. Verdine. 1994. Evidence for a non-α-helical DNA-binding motif in the Rel homology region. Proc. Natl. Acad. Sci. USA 91: 908–912.
   PubMedGoogle Scholar
• Ludwig, L., H. Kessler, M. Wagner, C. Hoang-Vu, H. Dralle, G. Adler, B. O. Bohm, and R. M. Schmid. 2001. Nuclear factor-κB is constitutively active in C-cell carcinoma and required for RET-induced transformation. Cancer Res. 61: 4526–4535.
   PubMedGoogle Scholar
• Luo, K. X., T. R. Hurley, and B. M. Sefton. 1991. Cyanogen bromide cleavage and proteolytic peptide mapping of proteins immobilized to membranes. Methods Enzymol. 201: 149–152.
   PubMedGoogle Scholar
• Madrid, L. V., M. W. Mayo, J. Y. Reuther, and A. S. Baldwin, Jr. 2001. Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. J. Biol. Chem. 276: 18934–18940.
   PubMed Web of Science ®Google Scholar
• Martin, A. G., and M. Fresno. 2000. TNFα activation of NF-κB requires the phosphorylation of Ser 471 in the transactivation domain of c-Rel. J. Biol. Chem. 275: 24383–24391.
   PubMedGoogle Scholar
• Mayo, M. W., C. Y. Wang, P. C. Cogswell, K. S. Rogers-Graham, S. W. Lowe, C. J. Der, and A. S. Baldwin. 1997. Requirement of NF-κB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278: 1812–1815.
   PubMed Web of Science ®Google Scholar
• Mosialos, G., P. Hamer, A. J. Capobianco, R. A. Laursen, and T. D. Gilmore. 1991. A protein kinase A recognition sequence is structurally linked to transformation by p59v-rel and cytoplasmic retention of p68c-rel . Mol. Cell. Biol. 11: 5867–5877.
   PubMedGoogle Scholar
• Muller, C. W., F. A. Rey, M. Sodeoka, G. L. Verdine, and S. C. Harrison. 1995. Structure of the NF-κB p50 homodimer bound to DNA. Nature 373: 311–317.
   PubMed Web of Science ®Google Scholar
• Nakayama, K., H. Shimizu, K. Mitomo, T. Watanabe, S.-I. Okamoto, and K.-I. Yamamoto. 1992. A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 κB-related motifs whose activities are repressed in lymphoid cells. Mol. Cell. Biol. 12: 1736–1746.
   PubMedGoogle Scholar
• Neiman, P. E., S. J. Thomas, and G. Loring. 1991. Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. Proc. Natl. Acad. Sci. USA 88: 5857–5861.
   PubMedGoogle Scholar
• Pahl, H. L. 1999. Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18: 6853–6866.
   PubMed Web of Science ®Google Scholar
• Park, I. C., S. H. Lee, D. Y. Whang, W. S. Hong, S. S. Choi, H. S. Shin, T. B. Choe, and S. I. Hong. 1997. Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. Anticancer Res. 17: 4619–4622.
   PubMedGoogle Scholar
• Rao, P. H., J. Houldsworth, K. Dyomina, N. Z. Parsa, J. C. Cigudosa, D. C. Louie, L. Popplewell, K. Offit, S. C. Jhanwar, and R. S. Chaganti. 1998. Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood 92: 234–240.
   PubMed Web of Science ®Google Scholar
• Rayet, B., and C. Gélinas. 1999. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18: 6938–6947.
   PubMed Web of Science ®Google Scholar
• Reuther, J. Y., G. W. Reuther, G. Cortez, A. M. Pendergast, and A. S. Baldwin, Jr. 1998. A requirement for NF-κB activation in Bcr-Abl-mediated transformation. Genes Dev. 12: 968–981.
   PubMed Web of Science ®Google Scholar
• Romero, P., and E. H. Humphries. 1995. A mutant v-rel with increased ability to transform B lymphocytes. J. Virol. 69: 301–307.
   PubMedGoogle Scholar
• Rosenwald, A., G. Wright, C. W. C., J. M. Conners, E. Campo, R. I. Fisher, R. D. Gascoyne, H. K. Muller-Hermelink, E. B. Smeland, J. M. H. Giltnane, E. M., H. Zhao, L. Averett, L. Yang, W. H. Wilson, E. S. Jaffe, R. Simon, R. D. Klausner, J. Powell, P. L. Duffey, D. L. Longo, T. C. Greiner, D. D. Weisenburger, W. G. Sanger, B. J. Dave, J. C. Lynch, J. Vose, J. O. Armitage, E. Montserrat, A. Lopez-Guillermo, T. M. Grogan, T. P. Miller, M. LeBlanc, G. Ott, S. Kvaloy, J. Delabie, H. Holte, P. Krajci, T. Stokke, and L. M. Staudt. 2002. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 346: 1937–1947.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• Sakurai, H., H. Chiba, H. Miyoshi, T. Sugita, and W. Toriumi. 1999. IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. J. Biol. Chem. 274: 30353–30356.
   PubMed Web of Science ®Google Scholar
• Sarma, V., Z. Lin, L. Clark, B. M. Rust, M. Tewari, R. J. Noelle, and V. M. Dixit. 1995. Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis. J. Biol. Chem. 270: 12343–12346.
   PubMed Web of Science ®Google Scholar
• Schafer, H., A. Arlt, A. Trauzold, A. Hunermann-Jansen, and W. E. Schmidt. 1999. The putative apoptosis inhibitor IEX-1L is a mutant nonspliced variant of p22(PRG1/IEX-1) and is not expressed in vivo. Biochem. Biophys. Res. Commun. 262: 139–145.
   PubMedGoogle Scholar
• Schilling, D., M. R. Pittelkow, and R. Kumar. 2001. IEX-1, an immediate early gene, increases the rate of apoptosis in keratinocytes. Oncogene 20: 7992–7997.
   PubMedGoogle Scholar
• Schreiber, E., P. Matthias, M. M. Muller, and W. Schaffner. 1989. Rapid detection of octamer binding proteins with “mini-extracts,” prepared from a small number of cells. Nucleic Acids Res. 17: 6419.
   PubMed Web of Science ®Google Scholar
• Sohur, U. S., C. L. Chen, D. J. Hicks, F. E. Yull, and L. D. Kerr. 2000. Nuclear factor-κB/Rel is apoptogenic in cytokine withdrawal-induced programmed cell death. Cancer Res. 60: 1202–1205.
   PubMedGoogle Scholar
• Sonenshein, G. E. 1997. Rel/NF-κB transcription factors and the control of apoptosis. Semin. Cancer Biol. 8: 113–119.
   PubMed Web of Science ®Google Scholar
• Song, H. Y., M. Rothe, and D. V. Goeddel. 1996. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-κB activation. Proc. Natl. Acad. Sci. USA 93: 6721–6725.
   PubMed Web of Science ®Google Scholar
• Stehlik, C., R. de Martin, I. Kumabashiri, J. A. Schmid, B. R. Binder, and J. Lipp. 1998. Nuclear factor (NF)-κB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J. Exp. Med. 188: 211–216.
   PubMed Web of Science ®Google Scholar
• Udalova, I. A., R. Mott, D. Field, and D. Kwiatkowski. 2002. Quantitative prediction of NF-κB DNA-protein interactions. Proc. Natl. Acad. Sci. USA 99: 8167–8172.
   PubMed Web of Science ®Google Scholar
• Van Antwerp, D. J., S. J. Martin, T. Kafri, D. R. Green, and I. M. Verma. 1996. Suppression of TNF-α-induced apoptosis by NF-κB. Science 274: 787–789.
   PubMed Web of Science ®Google Scholar
• Van Der Greer, P., K. Luo, B. M. Sefton, and T. Hunter. 1999. Phosphopeptide mapping and phosphoamino acid analysis on cellulose thin-layer plates, p. 97–126. In D. G. Hardie (ed.), Protein phosphorylation, 2nd ed. Oxford University Press, New York, N.Y.
   Google Scholar
• Walker, A. K., and P. J. Enrietto. 1996. Analysis of the role of v-rel in transcriptional regulation of high mobility group protein 14. Oncogene 12: 2515–2525.
   PubMedGoogle Scholar
• Wang, C. Y., M. W. Mayo, and A. S. Baldwin, Jr. 1996. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274: 784–787.
   PubMed Web of Science ®Google Scholar
• Wang, C. Y., M. W. Mayo, R. G. Korneluk, D. V. Goeddel, and A. S. Baldwin, Jr. 1998. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683.
   PubMed Web of Science ®Google Scholar
• Wang, D., and A. S. Baldwin, Jr. 1998. Activation of NF-κB-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of RelA/p65 on serine 529. J. Biol. Chem. 273: 29411–29416.
   PubMedGoogle Scholar
• Wang, D., S. D. Westerheide, J. L. Hanson, and A. S. Baldwin, Jr. 2000. Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J. Biol. Chem. 275: 32592–32597.
   PubMed Web of Science ®Google Scholar
• Watanabe, S., and H. M. Temin. 1983. Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. Mol. Cell. Biol. 3: 2241–2249.
   PubMed Web of Science ®Google Scholar
• Westerheide, S. D., M. W. Mayo, V. Anest, J. L. Hanson, and A. S. Baldwin, Jr. 2001. The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G1 transition. Mol. Cell. Biol. 21: 8428–8436.
   PubMed Web of Science ®Google Scholar
• White, D. W., and T. D. Gilmore. 1996. Bcl-2 and CrmA have different effects on transformation, apoptosis and the stability of IκB-α in chicken spleen cells transformed by temperature-sensitive v-Rel oncoproteins. Oncogene 13: 891–899.
   PubMedGoogle Scholar
• White, D. W., A. Roy, and T. D. Gilmore. 1995. The v-Rel oncoprotein blocks apoptosis and proteolysis of IκB-α in transformed chicken spleen cells. Oncogene 10: 857–868.
   PubMedGoogle Scholar
• Wu, M., H. Lee, R. E. Bellas, S. L. Schauer, M. Arsura, D. Katz, M. J. FitzGerald, T. L. Rothstein, D. H. Sherr, and G. E. Sonenshein. 1996. Inhibition of NF-κB/Rel induces apoptosis of murine B cells. EMBO J. 15: 4682–4690.
   PubMed Web of Science ®Google Scholar
• Wu, M. X., Z. Ao, K. V. S. Prasad, R. Wu, and S. F. Schlossman. 1998. IEX-1L, an apoptosis inhibitor involved in NF-κB-mediated cell survival. Science 281: 998–1001.
   PubMed Web of Science ®Google Scholar
• Xu, X., C. Prorock, H. Ishikawa, E. Maldonado, Y. Ito, and C. Gélinas. 1993. Functional interaction of the v-Rel and c-Rel oncoproteins with the TATA-binding protein and association with transcription factor IIB. Mol. Cell. Biol. 13: 6733–6741.
   PubMedGoogle Scholar
• You, M., and H. R. Bose, Jr. 1998. Identification of v-Rel oncogene-induced inhibitor of apoptosis by differential display. Methods 16: 373–385.
   PubMedGoogle Scholar
• You, M., P. T. Ku, R. Hrdlickova, and H. R. Bose, Jr. 1997. ch-IAP1, a member of the inhibitor-of-apoptosis protein family, is a mediator of the antiapoptotic activity of the v-Rel oncoprotein. Mol. Cell. Biol. 17: 7328–7341.
   PubMed Web of Science ®Google Scholar
• Zhong, H., R. E. Voll, and S. Ghosh. 1998. Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol. Cell 1: 661–671.
   PubMed Web of Science ®Google Scholar
• Zhou, P., L. J. Sun, V. Dotsch, G. Wagner, and G. L. Verdine. 1998. Solution structure of the core NFATC1/DNA complex. Cell 92: 687–696.
   PubMedGoogle Scholar
• Zong, W. X., L. C. Edelstein, C. Chen, J. Bash, and C. Gélinas. 1999. The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFα-induced apoptosis. Genes Dev. 13: 382–387.
   PubMed Web of Science ®Google Scholar
• Zong, W. X., M. Farrell, J. Bash, and C. Gélinas. 1997. v-Rel prevents apoptosis in transformed lymphoid cells and blocks TNFα-induced cell death. Oncogene 15: 971–980.
   PubMedGoogle Scholar