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. 1996 Nov;16(11):5974–5984. doi: 10.1128/mcb.16.11.5974

Basal phosphorylation of the PEST domain in the I(kappa)B(beta) regulates its functional interaction with the c-rel proto-oncogene product.

Z L Chu 1, T A McKinsey 1, L Liu 1, X Qi 1, D W Ballard 1
PMCID: PMC231600  PMID: 8887627

Abstract

The product of the c-rel proto-oncogene (c-Rel) belongs to the NF-kappaB/Rel family of polypeptides and has been implicated in the transcriptional control of cell proliferation and immune function. In human T lymphocytes, c-Rel is sequestered in the cytoplasmic compartment by constitutively phosphorylated inhibitors, including I(kappa)B(alpha) and I(kappa)B(beta). Studies with bacterially expressed forms of these inhibitory proteins revealed that unphosphorylated I(kappa)B(alpha) but not I(kappa)B(beta) assembles with c-Rel and inhibits its DNA binding activity. Furthermore, latent I(kappa)B(beta)-c-Rel complexes derived from mammalian cells were sensitive to phosphatase treatment, whereas I(kappa)B(alpha)-c-Rel complexes were resistant. We have identified a constitutive protein kinase in unstimulated T cells that associates with and phosphorylates I(kappa)B(beta) in vitro. The substrate specificity, electrophoretic mobility, and antigenic properties of this I(kappa)B(beta)-associated kinase (BAK) suggest identity with casein kinase II (CKII), an enzyme known to mediate basal phosphorylation of I(kappa)B(alpha). Phosphorylation of recombinant I(kappa)B(beta) by either BAK or CKII restored the capacity of this inhibitor to antagonize the DNA binding activity of c-Rel. Peptide mapping and mutational analyses localized the bulk of the basal phosphorylation sites in I(kappa)B(beta) to the C-terminal PEST domain, which contains two potential acceptors for CKII-mediated phosphoryl group transfer (Ser-313 and Ser-315). Point mutations introduced into the full-length inhibitor at Ser-313 and Ser-315 led to a significant reduction in the phosphorylation of I(kappa)B(beta) and severely impaired its c-Rel inhibitory function in vivo. Taken together, these findings strongly suggest that basal phosphorylation of the PEST domain of I(kappa)B(beta) at consensus CKII sites is required for the efficient formation of latent I(kappa)B(beta)-c-Rel complexes.

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Selected References

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  1. Abbadie C., Kabrun N., Bouali F., Smardova J., Stéhelin D., Vandenbunder B., Enrietto P. J. 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. 1993 Dec 3;75(5):899–912. doi: 10.1016/0092-8674(93)90534-w. [DOI] [PubMed] [Google Scholar]
  2. Alkalay I., Yaron A., Hatzubai A., Orian A., Ciechanover A., Ben-Neriah Y. Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10599–10603. doi: 10.1073/pnas.92.23.10599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andersson S., Davis D. L., Dahlbäck H., Jörnvall H., Russell D. W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989 May 15;264(14):8222–8229. [PubMed] [Google Scholar]
  4. Baldwin A. S., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. doi: 10.1146/annurev.immunol.14.1.649. [DOI] [PubMed] [Google Scholar]
  5. Ballard D. W., Böhnlein E., Hoffman J. A., Bogerd H. P., Dixon E. P., Franza B. R., Greene W. C. Activation of the interleukin-2 receptor alpha gene: regulatory role for DNA-protein interactions flanking the kappa B enhancer. New Biol. 1989 Oct;1(1):83–92. [PubMed] [Google Scholar]
  6. Ballard D. W., Dixon E. P., Peffer N. J., Bogerd H., Doerre S., Stein B., Greene W. C. The 65-kDa subunit of human NF-kappa B functions as a potent transcriptional activator and a target for v-Rel-mediated repression. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1875–1879. doi: 10.1073/pnas.89.5.1875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ballard D. W., Walker W. H., Doerre S., Sista P., Molitor J. A., Dixon E. P., Peffer N. J., Hannink M., Greene W. C. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Cell. 1990 Nov 16;63(4):803–814. doi: 10.1016/0092-8674(90)90146-6. [DOI] [PubMed] [Google Scholar]
  8. Barroga C. F., Stevenson J. K., Schwarz E. M., Verma I. M. Constitutive phosphorylation of I kappa B alpha by casein kinase II. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7637–7641. doi: 10.1073/pnas.92.17.7637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beg A. A., Baldwin A. S., Jr The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 1993 Nov;7(11):2064–2070. doi: 10.1101/gad.7.11.2064. [DOI] [PubMed] [Google Scholar]
  10. Beg A. A., Sha W. C., Bronson R. T., Baltimore D. Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice. Genes Dev. 1995 Nov 15;9(22):2736–2746. doi: 10.1101/gad.9.22.2736. [DOI] [PubMed] [Google Scholar]
  11. Blanar M. A., Rutter W. J. Interaction cloning: identification of a helix-loop-helix zipper protein that interacts with c-Fos. Science. 1992 May 15;256(5059):1014–1018. doi: 10.1126/science.1589769. [DOI] [PubMed] [Google Scholar]
  12. Boyle W. J., van der Geer P., Hunter T. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 1991;201:110–149. doi: 10.1016/0076-6879(91)01013-r. [DOI] [PubMed] [Google Scholar]
  13. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  14. Brockman J. A., Scherer D. C., McKinsey T. A., Hall S. M., Qi X., Lee W. Y., Ballard D. W. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. Mol Cell Biol. 1995 May;15(5):2809–2818. doi: 10.1128/mcb.15.5.2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Brown K., Gerstberger S., Carlson L., Franzoso G., Siebenlist U. Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. Science. 1995 Mar 10;267(5203):1485–1488. doi: 10.1126/science.7878466. [DOI] [PubMed] [Google Scholar]
  16. Bryan R. G., Li Y., Lai J. H., Van M., Rice N. R., Rich R. R., Tan T. H. Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells. Mol Cell Biol. 1994 Dec;14(12):7933–7942. doi: 10.1128/mcb.14.12.7933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Böhnlein E., Lowenthal J. W., Siekevitz M., Ballard D. W., Franza B. R., Greene W. C. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell. 1988 Jun 3;53(5):827–836. doi: 10.1016/0092-8674(88)90099-2. [DOI] [PubMed] [Google Scholar]
  18. Chen Z., Hagler J., Palombella V. J., Melandri F., Scherer D., Ballard D., Maniatis T. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 1995 Jul 1;9(13):1586–1597. doi: 10.1101/gad.9.13.1586. [DOI] [PubMed] [Google Scholar]
  19. Costello R., Lipcey C., Algarté M., Cerdan C., Baeuerle P. A., Olive D., Imbert J. Activation of primary human T-lymphocytes through CD2 plus CD28 adhesion molecules induces long-term nuclear expression of NF-kappa B. Cell Growth Differ. 1993 Apr;4(4):329–339. [PubMed] [Google Scholar]
  20. Cullen B. R. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol. 1987;152:684–704. doi: 10.1016/0076-6879(87)52074-2. [DOI] [PubMed] [Google Scholar]
  21. DiDonato J. A., Mercurio F., Karin M. Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B. Mol Cell Biol. 1995 Mar;15(3):1302–1311. doi: 10.1128/mcb.15.3.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. DiDonato J., Mercurio F., Rosette C., Wu-Li J., Suyang H., Ghosh S., Karin M. Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation. Mol Cell Biol. 1996 Apr;16(4):1295–1304. doi: 10.1128/mcb.16.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Doerre S., Sista P., Sun S. C., Ballard D. W., Greene W. C. The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1023–1027. doi: 10.1073/pnas.90.3.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. DuBridge R. B., Tang P., Hsia H. C., Leong P. M., Miller J. H., Calos M. P. Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol Cell Biol. 1987 Jan;7(1):379–387. doi: 10.1128/mcb.7.1.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ernst M. K., Dunn L. L., Rice N. R. The PEST-like sequence of I kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmic retention of c-Rel or RelA homodimers. Mol Cell Biol. 1995 Feb;15(2):872–882. doi: 10.1128/mcb.15.2.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Finco T. S., Baldwin A. S. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995 Sep;3(3):263–272. doi: 10.1016/1074-7613(95)90112-4. [DOI] [PubMed] [Google Scholar]
  27. Ganchi P. A., Sun S. C., Greene W. C., Ballard D. W. A novel NF-kappa B complex containing p65 homodimers: implications for transcriptional control at the level of subunit dimerization. Mol Cell Biol. 1993 Dec;13(12):7826–7835. doi: 10.1128/mcb.13.12.7826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ghosh P., Tan T. H., Rice N. R., Sica A., Young H. A. The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family: c-Rel, p50, and p65. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1696–1700. doi: 10.1073/pnas.90.5.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  30. Haskill S., Beg A. A., Tompkins S. M., Morris J. S., Yurochko A. D., Sampson-Johannes A., Mondal K., Ralph P., Baldwin A. S., Jr Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell. 1991 Jun 28;65(7):1281–1289. doi: 10.1016/0092-8674(91)90022-q. [DOI] [PubMed] [Google Scholar]
  31. Hathaway G. M., Lubben T. H., Traugh J. A. Inhibition of casein kinase II by heparin. J Biol Chem. 1980 Sep 10;255(17):8038–8041. [PubMed] [Google Scholar]
  32. Hibi M., Lin A., Smeal T., Minden A., Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993 Nov;7(11):2135–2148. doi: 10.1101/gad.7.11.2135. [DOI] [PubMed] [Google Scholar]
  33. Inoue J., Kerr L. D., Rashid D., Davis N., Bose H. R., Jr, Verma I. M. Direct association of pp40/I kappa B beta with rel/NF-kappa B transcription factors: role of ankyrin repeats in the inhibition of DNA binding activity. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333–4337. doi: 10.1073/pnas.89.10.4333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ito C. Y., Kazantsev A. G., Baldwin A. S., Jr Three NF-kappa B sites in the I kappa B-alpha promoter are required for induction of gene expression by TNF alpha. Nucleic Acids Res. 1994 Sep 11;22(18):3787–3792. doi: 10.1093/nar/22.18.3787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jaffray E., Wood K. M., Hay R. T. Domain organization of I kappa B alpha and sites of interaction with NF-kappa B p65. Mol Cell Biol. 1995 Apr;15(4):2166–2172. doi: 10.1128/mcb.15.4.2166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Janknecht R., de Martynoff G., Lou J., Hipskind R. A., Nordheim A., Stunnenberg H. G. Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8972–8976. doi: 10.1073/pnas.88.20.8972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kerr L. D., Inoue J., Davis N., Link E., Baeuerle P. A., Bose H. R., Jr, Verma I. M. The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation. Genes Dev. 1991 Aug;5(8):1464–1476. doi: 10.1101/gad.5.8.1464. [DOI] [PubMed] [Google Scholar]
  38. Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., Le Bail O., Urban M. B., Kourilsky P., Baeuerle P. A., Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. doi: 10.1016/0092-8674(90)90275-j. [DOI] [PubMed] [Google Scholar]
  39. Kuenzel E. A., Mulligan J. A., Sommercorn J., Krebs E. G. Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides. J Biol Chem. 1987 Jul 5;262(19):9136–9140. [PubMed] [Google Scholar]
  40. Kunsch C., Rosen C. A. NF-kappa B subunit-specific regulation of the interleukin-8 promoter. Mol Cell Biol. 1993 Oct;13(10):6137–6146. doi: 10.1128/mcb.13.10.6137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Köntgen F., Grumont R. J., Strasser A., Metcalf D., Li R., Tarlinton D., Gerondakis S. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes Dev. 1995 Aug 15;9(16):1965–1977. doi: 10.1101/gad.9.16.1965. [DOI] [PubMed] [Google Scholar]
  42. Lai J. H., Horvath G., Li Y., Tan T. H. Mechanisms of enhanced nuclear translocation of the transcription factors c-Rel and NF-kappa B by CD28 costimulation in human T lymphocytes. Ann N Y Acad Sci. 1995 Sep 7;766:220–223. doi: 10.1111/j.1749-6632.1995.tb26669.x. [DOI] [PubMed] [Google Scholar]
  43. Lai J. H., Tan T. H. CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin. J Biol Chem. 1994 Dec 2;269(48):30077–30080. [PubMed] [Google Scholar]
  44. Le Bail O., Schmidt-Ullrich R., Israël A. Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family. EMBO J. 1993 Dec 15;12(13):5043–5049. doi: 10.1002/j.1460-2075.1993.tb06197.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lee J. W., Choi H. S., Gyuris J., Brent R., Moore D. D. Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Mol Endocrinol. 1995 Feb;9(2):243–254. doi: 10.1210/mend.9.2.7776974. [DOI] [PubMed] [Google Scholar]
  46. Lin R., Beauparlant P., Makris C., Meloche S., Hiscott J. Phosphorylation of IkappaBalpha in the C-terminal PEST domain by casein kinase II affects intrinsic protein stability. Mol Cell Biol. 1996 Apr;16(4):1401–1409. doi: 10.1128/mcb.16.4.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Link E., Kerr L. D., Schreck R., Zabel U., Verma I., Baeuerle P. A. Purified I kappa B-beta is inactivated upon dephosphorylation. J Biol Chem. 1992 Jan 5;267(1):239–246. [PubMed] [Google Scholar]
  48. McElhinny J. A., Trushin S. A., Bren G. D., Chester N., Paya C. V. Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293, and T-291 and is required for its degradation. Mol Cell Biol. 1996 Mar;16(3):899–906. doi: 10.1128/mcb.16.3.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. McKinsey T. A., Brockman J. A., Scherer D. C., Al-Murrani S. W., Green P. L., Ballard D. W. Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB. Mol Cell Biol. 1996 May;16(5):2083–2090. doi: 10.1128/mcb.16.5.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Molitor J. A., Walker W. H., Doerre S., Ballard D. W., Greene W. C. NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10028–10032. doi: 10.1073/pnas.87.24.10028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Müller E., Boldyreff B., Scheidtmann K. H. Characterization of protein kinase activities associated with p53-large-T immune complexes from SV40-transformed rat cells. Oncogene. 1993 Aug;8(8):2193–2205. [PubMed] [Google Scholar]
  52. Nakayama K., Shimizu H., Mitomo K., Watanabe T., Okamoto S., Yamamoto K. A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells. Mol Cell Biol. 1992 Apr;12(4):1736–1746. doi: 10.1128/mcb.12.4.1736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Palombella V. J., Rando O. J., Goldberg A. L., Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773–785. doi: 10.1016/s0092-8674(94)90482-0. [DOI] [PubMed] [Google Scholar]
  54. Prickett K. S., Amberg D. C., Hopp T. P. A calcium-dependent antibody for identification and purification of recombinant proteins. Biotechniques. 1989 Jun;7(6):580–589. [PubMed] [Google Scholar]
  55. Rechsteiner M., Rogers S. W. PEST sequences and regulation by proteolysis. Trends Biochem Sci. 1996 Jul;21(7):267–271. [PubMed] [Google Scholar]
  56. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  57. Ruben S. M., Dillon P. J., Schreck R., Henkel T., Chen C. H., Maher M., Baeuerle P. A., Rosen C. A. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490–1493. doi: 10.1126/science.2006423. [DOI] [PubMed] [Google Scholar]
  58. Sachdev S., Rottjakob E. M., Diehl J. A., Hannink M. I kappa B-alpha-mediated inhibition of nuclear transport and DNA-binding by Rel proteins are separable functions: phosphorylation of C-terminal serine residues of I kappa B-alpha is specifically required for inhibition of DNA-binding. Oncogene. 1995 Sep 7;11(5):811–823. [PubMed] [Google Scholar]
  59. Sawada K., Krantz S. B., Kans J. S., Dessypris E. N., Sawyer S., Glick A. D., Civin C. I. Purification of human erythroid colony-forming units and demonstration of specific binding of erythropoietin. J Clin Invest. 1987 Aug;80(2):357–366. doi: 10.1172/JCI113080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Scherer D. C., Brockman J. A., Chen Z., Maniatis T., Ballard D. W. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11259–11263. doi: 10.1073/pnas.92.24.11259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schwarz E. M., Van Antwerp D., Verma I. M. Constitutive phosphorylation of IkappaBalpha by casein kinase II occurs preferentially at serine 293: requirement for degradation of free IkappaBalpha. Mol Cell Biol. 1996 Jul;16(7):3554–3559. doi: 10.1128/mcb.16.7.3554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  64. Sha W. C., Liou H. C., Tuomanen E. I., Baltimore D. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 1995 Jan 27;80(2):321–330. doi: 10.1016/0092-8674(95)90415-8. [DOI] [PubMed] [Google Scholar]
  65. Siebenlist U., Franzoso G., Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol. 1994;10:405–455. doi: 10.1146/annurev.cb.10.110194.002201. [DOI] [PubMed] [Google Scholar]
  66. Stein B., Rahmsdorf H. J., Steffen A., Litfin M., Herrlich P. UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein. Mol Cell Biol. 1989 Nov;9(11):5169–5181. doi: 10.1128/mcb.9.11.5169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Sun S., Elwood J., Greene W. C. Both amino- and carboxyl-terminal sequences within I kappa B alpha regulate its inducible degradation. Mol Cell Biol. 1996 Mar;16(3):1058–1065. doi: 10.1128/mcb.16.3.1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Suyang H., Phillips R., Douglas I., Ghosh S. Role of unphosphorylated, newly synthesized I kappa B beta in persistent activation of NF-kappa B. Mol Cell Biol. 1996 Oct;16(10):5444–5449. doi: 10.1128/mcb.16.10.5444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Tan T. H., Huang G. P., Sica A., Ghosh P., Young H. A., Longo D. L., Rice N. R. Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel. Mol Cell Biol. 1992 Sep;12(9):4067–4075. doi: 10.1128/mcb.12.9.4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Thanos D., Maniatis T. NF-kappa B: a lesson in family values. Cell. 1995 Feb 24;80(4):529–532. doi: 10.1016/0092-8674(95)90506-5. [DOI] [PubMed] [Google Scholar]
  71. Thompson J. E., Phillips R. J., Erdjument-Bromage H., Tempst P., Ghosh S. I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell. 1995 Feb 24;80(4):573–582. doi: 10.1016/0092-8674(95)90511-1. [DOI] [PubMed] [Google Scholar]
  72. Traenckner E. B., Pahl H. L., Henkel T., Schmidt K. N., Wilk S., Baeuerle P. A. Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli. EMBO J. 1995 Jun 15;14(12):2876–2883. doi: 10.1002/j.1460-2075.1995.tb07287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Verma I. M., Stevenson J. K., Schwarz E. M., Van Antwerp D., Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995 Nov 15;9(22):2723–2735. doi: 10.1101/gad.9.22.2723. [DOI] [PubMed] [Google Scholar]
  74. Weih F., Carrasco D., Durham S. K., Barton D. S., Rizzo C. A., Ryseck R. P., Lira S. A., Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995 Jan 27;80(2):331–340. doi: 10.1016/0092-8674(95)90416-6. [DOI] [PubMed] [Google Scholar]
  75. Whiteside S. T., Ernst M. K., LeBail O., Laurent-Winter C., Rice N., Israël A. N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity. Mol Cell Biol. 1995 Oct;15(10):5339–5345. doi: 10.1128/mcb.15.10.5339. [DOI] [PMC free article] [PubMed] [Google Scholar]

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