Rel/NF-κB/IκB family: Intimate tales of association and dissociation

Genes and Development

Volumn 9, Issue 22, 1995, Pages 2723-2735

  Verma, Inder M ^a   Stevenson, Jennifer K ^a   Schwarz, Edward M ^a   Van Antwerp, Daniel ^a   Miyamoto, Shigeki ^a,b  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHOTRANSFERASE; TRANSCRIPTION FACTOR;

CELL FUNCTION; ENZYME REGULATION; GENE ACTIVATION; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; HUMAN; INTRACELLULAR TRANSPORT; MULTIGENE FAMILY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DNA BINDING; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; VIRUS TRANSCRIPTION;

EID: 0028971289     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.9.22.2723     Document Type: Review

References (114)

1. Alkalay, I., A. Yaron, A. Hatzubai, S. Jung, A. Avraham, O. Gerlitz, I. Pashutlavon, and Y. Benneriah. 1995. In vivo stimulation of IκB phosphorylation is not sufficient to activate NF-κB. Mol. Cell Biol. 15: 1294-1301.
2. 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.
3. Auphan, N., J.A. DiDonato, C. Rosette, A. Helmberg, and M. Karin. 1995. Immunosuppression by glucocorticoids: Inhibition of NF-κB activity through induction of IκB synthesis. Science 270: 286-290.
4. Baeuerle, P.A. 1991. The inducible transcription activator NF-κB - Regulation by distinct protein subunits. Biochim. Biophys. Acta 1072: 63-80.
5. Baeuerle, P.A. and D. Baltimore. 1989. A 65-kD subunit of active NF-κB is required for inhibition of NF-κB by IκB. Genes & Dev. 3:1689-1698.
6. Baeuerle, P.A. and T. Henkel. 1994. Function and activation of NF-κB in the immune system. Annu. Rev. Immunol. 12:141-179.
7. Baeuerle, P.A., M, Lenardo, J. W. Pierce, and D. Baltimore. 1988. Phorbol-ester-induced activation of the NF-κB transcription factor involves dissociation of an apparently cytoplasmic NF-κB/inhibitor complex. Cold Spring Harbor Symp. Quant. Biol. 53: 789-798.
8. Barroga, C.F., J.K. Stevenson, E.M. Schwarz, and I.M. Verma. 1995. Constitutive phosphorylation of IκBα by casein kinase II. Proc. Natl Acad. Sci 92: 7637-7641.
9. Beg, A.A. and A.S. Baldwin. 1993. The IκB proteins - Multifunctional regulators of Rel/NF-κB transcription factors. Genes & Dev. 7:2064-2070.
10. Beg, A.A., T.S. Finco, P.V. Nantermet, and A.S. Baldwin. 1993. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IκBα - A mechanism for NF-κB activation. Mol. Cell. Biol. 13: 3301-3310.
11. Beg, A.A., W.C. Sha, R.T. Bronson, S. Ghosh, and D. Baltimore. 1995a. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376: 167-170.
12. Beg, A.A., W.C. Sha, R.T. Bronson, and D. Baltimore. 1995b. Constitutive NF-κB activation, enhanced granulopoiesis and neonatal lethality in IκBα-deficient mice. Genes &. Dev., this issue.
13. Belvin, M.P., Y. Jin, and K.V. Anderson. 1995. Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes &. Dev. 9: 783-793.
14. Bours, V., I. Villalobos, P.R. Burd, K. Kelly, and U. Siebenlist. 1990. Cloning of a mitogen-inducible gene encoding a κB DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. Nature 348: 76-80.
15. Bours, V., P.R. Burd, K. Brown, J. Villalobos, S. Park, R.P. Ryseck, R. Bravo, K. Kelly, and U. Siebenlist. 1992. A novel mitogen-inducible gene product related to p50/p105-NF-κB participates in transactivation through a κB site. Mol. Cell. Biol. 12: 685-695.
16. Brockman, J.A., D.C. Scherer, T.A. McKinsey, S.M. Hall, X.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: 2809-2818.
17. Brown, K., S. Park, T. Kanno, G. Franzoso, and U. Siebenlist. 1993. Mutual regulation of the transcriptional activator NF-κB and its inhibitor, IκBα. Proc. Natl. Acad. Sci. 90: 2532-2536.
18. Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist. 1995. Control of IκBα proteolysis by site-specific, signal induced phosphorylation. Science 267: 1485-1488.
19. Burkly, L., C. Hession, L. Ogata, C. Reilly, L.A. Marconi, D. Olson, R. Tizard, R. Cate, and D. Lo. 1995. Expression of RelB is required for the development of thymic medulla and dendritic cells. Nature 373: 531-536.
20. Chen, Z.J., 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.
21. Chiao, P.J., S. Miyamoto, and I.M. Verma. 1994. Autoregulation of IκBα activity. Proc. Natl. Acad. Sci. 91: 22-32.
22. Coleman, T.A., C. Kunsch, M. Maher, S.M. Ruben, and C.A. Rosen. 1993. Acquisition of NF-κB1-selective DNA binding by substitution of four amino acid residues from NF-κB1 into RelA. Mol. Cell. Biol. 13: 3850-3859.
23. Collins, T., M.A. Read, A.S. Neish, M.Z. Whitley, D. Thanos, and T. Maniatis. 1995. Transcriptional regulation of endothelial cell adhesion molecules - NF-κB and cytokine-inducible enhancers. FASEB J. 9: 899-909.
24. Cordle, S.R., R. Donald, M.A. Read, and J. Hawiger. 1993. Lipopolysaccharide induces phosphorylation of MAD3 and activation of C-Rel and related NF-κB proteins in human monocytic THP-1 cells. J. Biol. Chem. 268: 11803-11810.
25. Davis, N., S. Ghosh, D.L. Simmons, P. Tempst, H.-C. Liou, D. Baltimore, and H.R. Bose Jr. 1991. Rel-associated pp40: An inhibitor of the Rel family of transcription factors. Science 253: 1268-1271.
26. Didonato, J.A., F. Mercurio, and M. Karin. 1995. Phosphorylation of IκBα precedes but is not sufficient for its dissociation from NF-κB. Mol. Cell. Biol. 15: 1302-1311.
27. Dobrzanski, P., R.-P. Ryseck, and R. Bravo. 1993. Both N- and C-terminal domains of RelB are required for full transactivation: Role of the N-terminal leucine zipper-like motif. Mol. Cell. Biol. 13: 1572-1582.
28. _. 1994. Differential interactions of Rel-NF-κB complexes with IκBα determine pools of constitutive and inducible NF-κB activity. EMBO J. 13: 4608-4616.
29. Ernst, M.K., L.L. Dunn, and N.R. Rice. 1995. The PEST-like sequence of IκBα is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA. Mol. Cell Biol. 15: 872-882.
30. Finco, T.S., A.A. Beg, and A.S. Baldwin. 1994. Inducible phosphorylation of IκBα is not sufficient for its dissociation from NF-κB and is inhibited by protease inhibitors. Proc. Natl. Acad. Sci. 91: 11884-11888.
31. Franzoso, G., V. Bours, S. Park, M. Tomitayamaguchi, K. Kelly, and U. Siebenlist. 1992. The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-κB-mediated inhibition. Nature 359:339-342.
32. Fujita, T., G.P. Nolan, H.C. Liou, M.L. Scott, and D. Baltimore. 1993. The candidate proto-oncogene Bcl-3 encodes a transcriptional coactivator that activates through NF-κB p50 homodimers. Genes & Dev. 7: 1354-1363.
33. Ganchi, P.A., S.C. Sun, W.C. Greene, and D.W. Ballard. 1993. A novel NF-κB complex containing p65 homodimers - implications for transcriptional control at the level of subunit dimerization. Mol. Cell. Biol 13: 7826-7835.
34. Ghosh, G., G. Vanduyne, S. Ghosh, and P.B. Sigler. 1995. Structure of NF-κB p50 homodimer bound to a κB site. Nature 373: 303-310.
35. Ghosh, S. and D. Baltimore. 1990. Activation in vitro of NF-κB by phosphorylation of its inhibitor IκB. Nature 344:678-682.
36. Ghosh, S., A.M. Gifford, L.R. Riviere, P. Tempst, G.P. Nolan, and D. Baltimore. 1990. Cloning of the p50 DNA binding subunit of NF-κB - Homology to Rel and Dorsal. Cell 62: 1019-1029.
37. Grilli, M., A. Chentran, and M.J. Lenardo. 1993. Tumor necrosis factor-alpha mediates a T-cell receptor-independent induction of the gene regulatory factor NF-κB in T-lymphocytes. Mol. Immunol. 30: 1287-1294.
38. Grumont, R.J. and S. Gerondakis. 1994a. Alternative splicing of RNA transcripts encoded by the murine p105 NF-κB gene generates IκBγ isoforms with different inhibitory activities. Proc. Natl. Acad. Sci. 91: 4367-4371.
39. _. 1994b. The subunit composition of NF-κB complexes changes during B-cell development. Cell Growth & Differ-5: 1321-1331.
40. Grumont R.J., f. Fecondo, and S. Gerondakis. 1994. Alternate RNA splicing of murine nfkb1 generates a nuclear isoform of the p50 precursor NF-κB1 that can function as a transactivator of NF-κB-regulated transcription. Mol. Cell. Biol. 14: 8460-8470.
41. Haskill, S., A.A. Beg, S.M. Tompkins, J.S. Morris, A.D. Yurochko, A. Sampson-Johannes, K. Mondai, P. Ralph, and A.S. Baldwin Jr. 1991. Characterization of an immediate-early gene induced in adherent monocytes that encodes IκB-like activity. Cell 65: 1281-1289.
42. Hatada, E.N., M. Naumann, and C. Scheidereit. 1993. Common structural constituents confer IκB activity to NF-κB p105 and IκB/MAD-3. EMBO J. 12: 2781-2788.
43. Hayashi, T., T. Sekine, and T. Okamoto. 1993. Identification of a new serine kinase that activates NF-κB by direct phosphorylation. J. Biol. Chem. 268: 26790-26795.
44. Henkel, T., T. Machleidt, I. Alkalay, M. Kronke, Y. Benneriah, and P.A. Baeuerle. 1993. Rapid proteolysis of IκBα is necessary for activation of transcription factor NF-κB. Nature 365: 182-185.
45. Higgins, K.A., J.R. Perez, T.A. Coleman, K. Dorshkind, W.A. McComas, U.M. Sarmiento, C.A. Rosen, and R. Narayanan. 1993. Antisense inhibition of the p65 subunit of NF-κB blocks tumorigenicity and causes tumor regression. Proc. Natl. Acad. Sci. 90: 9901-9905.
46. Hsu, H.L., J. Xiong, and D.V. Goeddel. 1995. The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation. Cell 81: 495-504.
47. Inoue, J., L.D. Kerr, A. Kakizuka, and I.M. Verma. 1992. IκBγ, a 70 kD protein identical to the C-terminal half of p110 NF-κB - A new member of the IκB family. Cell 68: 1109-1120.
48. Israel, A. 1995. A role for phosphorylation and degradation in the control of NF-κB activity. Trends Genet. 11: 203-205.
49. + T lymphocytes. Science 256: 1452-1456.
50. Kerr, L.D., J.-I. Inoue, N. Davis, E. Link, P.A. Baeuerle, H.R. Bose Jr., and I.M. Verma. 1991. The Rel-associated pp40 protein prevents DNA binding of rel and NF-κB - Relationship with IκBβ and regulation by phosphorylation. Genes & Dev. 5: 1464-1476.
51. Kerr, L.D., L.J. Ransone, P. Wamsley, M.J. Schmitt, T.G. Boyer, Q. Zhou, A.J. Berk, and I.M. Verma. 1993. Association be tween proto-oncoprotein Rel and TATA-binding protein mediates transcriptional activation by NF-κB. Nature 365:412-419.
52. Kieran, M., V. Blank, F. Logeat, J. Vandekerckhove, F. Lottspeich, O. Lebail, M.B. Urban, P. Kourilsky, P.A. Baeuerle, and A. Israel. 1990. The DNA binding subunit of NF-κB is identical to factor κBF1 and homologous to the Rel oncogene product. Cell 62: 1007-1018.
53. Kitajima, I., T. Shinohara, J. Bilakovics, D.A. Brown, X. Xu, and M. Nerenberg. 1992. Ablation of transplanted HTLV-I tax-transformed tumors in mice by antisense inhibition of NF-κB. Science 258: 1792-1795.
54. Kontgen, F., R.J. Grumont, A. Strasser, D. Metcalf, R. Li, D. Tarlinton, and S. Gerondakis. 1995. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity and interleukin-2 expression. Genes & Dev. 9: 1965-1977.
55. Kopp, E.B. and S. Ghosh. 1995. NF-κB and Rel proteins in innate immunity. Adv. Immunol. 58: 1-27.
56. Lehming, N., D. Thanos, J.M. Brickman, J. Ma, T. Maniatis, and M. Ptashne. 1994. An HMG-like protein that can switch a transcriptional activator to a repressor. Nature 371: 175-179.
57. Leveillard, T. and I.M. Verma. 1993. Diverse molecular mechanisms of inhibition of NF-κB/DNA binding complexes by IκB proteins. Gene Expression 3: 135-150.
58. Li, C.C., M. Korner, D.K. Ferris, E. Chen, R.M. Dai, and D.L. Longo. 1994. NF-κB/Rel family members are physically associated phosphoproteins. Biochem J. 303: 499-506.
59. Lin, Y.Z., S.Y. Yao, R.A. Veach, T.R. Torgerson, and J. Hawiger. 1995. Inhibition of nuclear translocation of transcription factor NF-κB by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J. Biol. Chem. 270: 14255-14258.
60. Liou, H.C., W.C. Sha, M.L. Scott, and D. Baltimore. 1994. Sequential induction of NF-κB/Rel family proteins during B-cell terminal differentiation. Mol. Cell. Biol. 14: 5349-5359.
61. Mellits, K.H., R.T. Hay, and S. Goodbourn. 1993. Proteolytic degradation of MAD3 (IκBα) and enhanced processing of the NF-κB precursor p105 are obligatory steps in the activation of NF-κB. Nucleic Acids Res. 21: 5059-5066.
62. Mercurio, F., J. DiDonato, C. Rosette, and M. Karin. 1992. Molecular cloning and characterization of a novel Rel/NF-κB family member displaying structural and functional homology to NF-κB p50-p105. DNA Cell Biol. 11: 523-537.
63. _. 1993. p105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction. Genes & Dev. 7: 705-718.
64. Meyer, R., E.N. Hatada, H.P. Hohmann, M. Haiker, C. Bartsch, U. Rothlisberger, H.W. Lahm, E.J. Schlaeger, A.P. van Loon, and C. Scheidereit et al. 1991. Cloning of the DNA-binding subunit of human nuclear factor κB: The level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor a. Proc. Natl. Acad, Sci. 88: 966-970.
65. Miyamoto, S. and I.M. Verma. 1995. Rel/NF-κB/IκB story. Adv. Cancer Res. 66: 255-292.
66. Miyamoto, S., P.J. Chiao, and L.M. Verma. 1994a. Enhanced IκBα degradation is responsible for constitutive NF-κB activity in mature murine B-cell lines. Mol. Cell. Biol. 14: 3276-3282.
67. Miyamoto, S., M. Maki, M.J. Schmitt, M. Hatanaka, and I.M. Verma. 1994b. Tumor necrosis factor α-induced phosphorylation of IκBα is a signal for its degradation but not dissociation from NF-κB. Proc. Natl. Acad. Sci. 91: 12740-12744.
68. Miyamoto, S., M.J. Schmitt, and I.M. Verma. 1994c. Qualitative changes in the subunit composition of κB binding complexes during murine B cell differentiation. Proc. Natl. Acad. Sci. 91: 5056-5060.
69. 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.
70. 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.
71. Narayanan, R., K.A. Higgins, J.R. Perez, T.A. Coleman, and C.A. Rosen. 1993. Evidence for differential functions of the p50 and p65 subunits of NF-κB with a cell adhesion model. Mol. Cell. Biol. 13: 3802-3810.
72. Naumann, M. and C. Scheidereit. 1994. Activation of NF-κB in vivo is regulated by multiple phosphorylations. EMBO J. 13: 4597-4607.
73. Naumann, M., F.G. Wulczyn, and C. Scheidereit. 1993. The NF-κB precursor p105 and the proto-oncogene product Bcl-3 are IκB molecules and control nuclear translocation of NF-κB. EMBO J. 12: 213-222.
74. Neri, A., C.C. Chang, L. Lombardi, M. Salina, P. Corradini, A.T. Maiolo, R.S. K. Chaganti, and R. Dalla-Favera. 1991. B-Cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50. Cell 67: 1075-1087.
75. Nolan, G.P. 1994. NF-AT-AP-1 and Rel-Bzip - Hybrid vigor and binding under the influence. Cell 77: 795-798.
76. Nolan, G.P. and D. Baltimore. 1992. The inhibitory ankyrin and activator Rel proteins. Curr. Opin. Genet. Dev. 2: 211-220.
77. Nolan, G.P., S. Ghosh, H.C. Liou, P. Tempst, and D. Baltimore. 1991. DNA binding and IκB inhibition of the cloned p65 subunit of NF-κB, a Rel-related polypeptide. Cell 64: 961-969.
78. Nolan, G.P., T. Fujita, K. Bhatia, C. Huppi, H.C. Liou, M.L. Scott, and D. Baltimore. 1993. The Bcl-3 proto-oncogene encodes a nuclear IκB-like molecule that preferentially interacts with NF-κB p50 and P52 in a phosphorylation-dependent manner. Mol. Cell. Biol. 13: 3557-3566.
79. Norris, J.L. and J.L. Manley. 1992. Selective nuclear transport of the Drosophila morphogen dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A. Genes & Dev. 6: 1654-1667.
80. Ohno, H., G. Takimoto, and T.W. McKeithan. 1990. The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell 60: 991-997.
81. Palombella, V.J., O.J. Rando, A.L. Goldberg, and T. Maniatis. 1994. The ubiquitin-proteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB. Cell 78: 773-785.
82. Ray, A., M.D. Siegel, K.E. Prefontaine, and P. Ray. 1995. Antiinflammation - Direct physical association and functional antagonism between transcription factor NF-κB and the glucocorticoid receptor. Chest (Suppl.) 107: S139-S139.
83. Rechsteiner, M. 1990. PEST sequences are signals for rapid intracellular proteolysis. Semin. Cell Biol. 1: 433-440.
84. Rice, N.R. and M.K. Ernst. 1993. In vivo control of NF-κB activation by IκBα. EMBO J. 12: 4685-4695.
85. Rice, N.R., M.L. Mackichan, and A. Israel. 1992. The precursor of NF-κB p50 has IκB-like functions. Cell 71: 243-253.
86. Rodriguez, M.S., I. Michalopoulos, F. Arenzana-Seisdedos and R.T. Hay. 1995. Inducible degradation of IκBα in vitro and in vivo requires the acidic C-terminal domain of the protein. Mol. Cell. Biol. 15: 2413-2419.
87. Ruben, S.M., P.J. Dillon, R. Schreck, T. Henkel, C.H. Chen, M. Maher, P.A. Baeuerle, and C.A. Rosen. 1991. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-κB. Science 251: 1490-1493.
88. Ruben, S.M., J.F. Klement, T.A. Coleman, M. Maher, C.H. Chen, and C.A. Rosen. 1992. I-Rel - A novel Rel-related protein that inhibits NF-κB transcriptional activity. Genes & Dev. 6: 745-760.
89. Ryseck, R.P., P. Bull, M. Takamiya, V. Bours, U. Siebenlist, P. Dobrzanski, and R. Bravo. 1992. RelB, a new Rel family transcription activator that can interact with p50-NF-κB. Mol. Cell. Biol. 12: 674-684.
90. Scheinman, R.I., P.G. Cogswell, A.K. Lofquist, and A.S. Baldwin Jr. 1995. Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids. Science 270: 283-286.
91. Scherer, D.C., J.A. Brockman, Z. Chen, T. Maniatis, and D.W. Ballard. 1995. Signal-induced degradation of IκBα requires site-specific ubiquination. Proc. Natl. Acad. Sci. 92: 11259-11263.
92. Schmid, R.M., N.D. Perkins, C.S. Duckett, P.C. Andrews, and G.J. Nabel. 1991. Cloning of an NF-κB subunit which stimulates HIV transcription in synergy with p65. Nature 352: 733-736.
93. Schmitz, M.L. and P.A. Baeuerle. 1991. The p65 subunit is responsible for the strong transcription activating potential of NF-κB. EMBO J. 10: 3805-3817.
94. Schreck, R., H. Zorbas, E.L. Winnacker, and P.A. Baeuerle. 1990. The NF-κB transcription factor induces DNA bending which is modulated by its 65-kD subunit. Nucleic Acids Res. 18: 6497-6502.
95. Schreck, R., P. Rieber, and P.A. Baeuerle. 1991. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J. 10: 2247-2258.
96. Scott, M.L., T. Fujita, H.C. Liou, G.P. Nolan, and D. Baltimore. 1993. The p65 -subunit of NF-κB regulates IκB by two distinct mechanisms. Genes & Dev. 7: 1266-1276.
97. Sen, R. and D. Baltimore. 1986. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46: 705-716.
98. Sha, W.C., H.C. Liou, E.I. Tuomanen, and D. Baltimore. 1995. Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses. Cell 80: 321-330.
99. Shirakawa, F. and S.B. Mizel. 1989. In vitro activation and nuclear translocation of NF-κB catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol. Cell. Biol. 9: 2424-2430.
100. Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol. 10: 405-455.
101. Stephens, R.M., N.R. Rice, R.R. Hiebsch, and H.R. Bose Jr. 1983. Nucleotide sequence of v-rel: The oncogene of the reticuloendotheliosis virus. Proc. Natl. Acad. Sci. 80: 6229-6232.
102. Steward, R. 1987. Dorsal, an embryonic polarity gene in Drosophila is homologous to the vertebrate proto-oncogene, c-rel. Science 238: 692-694.
103. Sun, S.C., P.A. Ganchi, D.W. Ballard, and W.C. Greene. 1993. NF-κB controls expression of inhibitor IκBα - Evidence for an inducible autoregulatory pathway. Science 259: 1912-1915.
104. Sun, S.C., P.A. Ganchi, C. Beraud, D.W. Ballard, and W.C. Greene. 1994. Autoregulation of the NF-κB transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc. Nati. Acad. Sci. 91: 1346-1350.
105. Thanos, D. and T. Maniatis. 1992. The high mobility group protein HMG-I(Y) is required for NF-κB-dependent virus induction of the human IFN-β gene. Cell 71: 777-789.
106. _. 1995. NF-κB - A lesson in family values. Cell 80: 529-532.
107. Thompson, J.E., R.J. Phillips, H. Erdjumentbromage, P. Tempst, and S. Ghosh. 1995. IκBβ regulates the persistent response in a biphasic activation of NF-κB. Cell 80: 573-582.
108. Traenckner, E.B., S. Wilk, and P.A. Baeuerle. 1994. A protea-some inhibitor prevents activation of NF-κB and stabilizes a newly phosphorylated form of κB that is still bound to NF-κB. EMBO J. 13: 5433-5441.
109. Traenckner, E.B.M., H.L. Pahl, T. Henkel, K.N. Schmidt, S. Wilk, and P.A. Baeuerle. 1995. Phosphorylation of human IκBα on serines 32 and 36 controls IκBα proteolysis and NF-κB activation in response to diverse stimuli. EMBO J. 14:2876-2883.
110. Wang, X.D., R. Sato, M.S. Brown, X.X. Hua, and J.L. Goldstein. 1994. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77: 53-62.
111. Weih, F., D. Carrasco, S.K. Durham, D.S. Barton, C.A. Rizzo, R.P. Ryseck, S.A. Lira, and R. Bravo. 1995. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/Rel family. Cell 80: 331-340.
112. Whiteside, S.T., M.K. Ernst, O. LeBail, C. Laurent-Winter, N. Rice, and A. Israël. 1995. N- and C-terminal sequences control degradation of MAD3/IκBα in response to inducers of NF-κB activity. Mol. Cell. Biol. 15: 5339-5345.
113. Xu, X., C. Prorock, H. Ishikawa, and E. Maldonado. 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.
114. Zabel, U., T. Henkel, M.D. 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.