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. 1996 Apr;16(4):1401–1409. doi: 10.1128/mcb.16.4.1401

Phosphorylation of IkappaBalpha in the C-terminal PEST domain by casein kinase II affects intrinsic protein stability.

R Lin 1, P Beauparlant 1, C Makris 1, S Meloche 1, J Hiscott 1
PMCID: PMC231124  PMID: 8657113

Abstract

The NF-kappaB/Rel transcription factors participate in the activation of immune system regulatory genes and viral early genes including the human immunodeficiency virus type 1 long terminal repeat. NF-kappaB/Rel proteins are coupled to inhibitory molecules, collectively termed IkappaB, which are responsible for cytoplasmic retention of NF-kappaB. Cell activation leads to the phosphorylation and degradation of IkappaBalpha, permitting NG-kappaB/Rel translocation to the nucleus and target gene activation. To further characterize the signaling events that contribute to IkappaBalpha phosphorylation, a kinase activity was isolated from Jurkat T cells that specifically interacted with IkappaBalpha in an affinity chromatography step and phosphorylated IkappaBalpha with high specificity in vitro. By using an in-gel kinase assay with recombinant IkappaBalpha as substrate, two forms of the kinase (43 and 38 kDa) were identified. Biochemical criteria and immunological cross-reactivity identified the kinase activity as the alpha catalytic subunit of casein kinase II (CKII). Deletion mutants of IkappaBalpha delta1 to delta4) localized phosphorylation to the C-terminal PEST domain of IkappaBalpha. Point mutation of residues T-291, S-283, and T-299 dramatically reduced phosphorylation of IkappaBalpha by the kinase in vitro. NIH-3T3 cells that stably expressed wild-type IkappaBalpha (wtIkappaB), double-point-mutated IkappaBalpha (T291A, S283A), or triple-point-mutated IkappaBalpha (T291A, S283A, T299A) under the control of the tetracycline-responsive promoter were generated. Constitutive phosphorylation of the triple point mutant was eliminated in vivo, although tumor necrosis factor-inducible IkappaBalpha degradation was unaffected. In cell lines and in transiently transfected cells, mutation of the CKII sites in IkappaBalpha resulted in a protein with increased intrinsic stability. Together with results demonstrating a role for N-terminal sites in inducer-mediated phosphorylation and degradation of IkappaBalpha, these studies indicate that CKII sites in the C-terminal PEST domain are important for constitutive phosphorylation and intrinsic stability of IkappaBalpha.

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Selected References

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  1. Baeuerle P. A., Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–217. doi: 10.1016/0092-8674(88)90382-0. [DOI] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Beauparlant P., Kwan I., Bitar R., Chou P., Koromilas A. E., Sonenberg N., Hiscott J. Disruption of I kappa B alpha regulation by antisense RNA expression leads to malignant transformation. Oncogene. 1994 Nov;9(11):3189–3197. [PubMed] [Google Scholar]
  5. 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]
  6. Beg A. A., Finco T. S., Nantermet P. V., Baldwin A. S., Jr Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol. 1993 Jun;13(6):3301–3310. doi: 10.1128/mcb.13.6.3301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beg A. A., Ruben S. M., Scheinman R. I., Haskill S., Rosen C. A., Baldwin A. S., Jr I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention. Genes Dev. 1992 Oct;6(10):1899–1913. doi: 10.1101/gad.6.10.1899. [DOI] [PubMed] [Google Scholar]
  8. Bours V., Burd P. R., Brown K., Villalobos J., Park S., Ryseck R. P., Bravo R., Kelly K., Siebenlist U. A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. Mol Cell Biol. 1992 Feb;12(2):685–695. doi: 10.1128/mcb.12.2.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bours V., Villalobos J., Burd P. R., Kelly K., Siebenlist U. Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. Nature. 1990 Nov 1;348(6296):76–80. doi: 10.1038/348076a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Brown K., Park S., Kanno T., Franzoso G., Siebenlist U. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532–2536. doi: 10.1073/pnas.90.6.2532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Brownell E., Mittereder N., Rice N. R. A human rel proto-oncogene cDNA containing an Alu fragment as a potential coding exon. Oncogene. 1989 Jul;4(7):935–942. [PubMed] [Google Scholar]
  14. 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]
  15. Cooper J. A., Sefton B. M., Hunter T. Detection and quantification of phosphotyrosine in proteins. Methods Enzymol. 1983;99:387–402. doi: 10.1016/0076-6879(83)99075-4. [DOI] [PubMed] [Google Scholar]
  16. Cordle S. R., Donald R., Read M. A., Hawiger J. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. J Biol Chem. 1993 Jun 5;268(16):11803–11810. [PubMed] [Google Scholar]
  17. 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]
  18. Duckett C. S., Perkins N. D., Kowalik T. F., Schmid R. M., Huang E. S., Baldwin A. S., Jr, Nabel G. J. Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3). Mol Cell Biol. 1993 Mar;13(3):1315–1322. doi: 10.1128/mcb.13.3.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Filhol O., Baudier J., Delphin C., Loue-Mackenbach P., Chambaz E. M., Cochet C. Casein kinase II and the tumor suppressor protein P53 associate in a molecular complex that is negatively regulated upon P53 phosphorylation. J Biol Chem. 1992 Oct 15;267(29):20577–20583. [PubMed] [Google Scholar]
  20. Finco T. S., Baldwin A. S., Jr Kappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1. J Biol Chem. 1993 Aug 25;268(24):17676–17679. [PubMed] [Google Scholar]
  21. Garoufalis E., Kwan I., Lin R., Mustafa A., Pepin N., Roulston A., Lacoste J., Hiscott J. Viral induction of the human beta interferon promoter: modulation of transcription by NF-kappa B/rel proteins and interferon regulatory factors. J Virol. 1994 Aug;68(8):4707–4715. doi: 10.1128/jvi.68.8.4707-4715.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. doi: 10.1038/344678a0. [DOI] [PubMed] [Google Scholar]
  23. Ghosh S., Gifford A. M., Riviere L. R., Tempst P., Nolan G. P., Baltimore D. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990 Sep 7;62(5):1019–1029. doi: 10.1016/0092-8674(90)90276-k. [DOI] [PubMed] [Google Scholar]
  24. Gilmore T. D. Malignant transformation by mutant Rel proteins. Trends Genet. 1991 Oct;7(10):318–322. doi: 10.1016/0168-9525(91)90421-l. [DOI] [PubMed] [Google Scholar]
  25. Gilmore T. D., Morin P. J. The I kappa B proteins: members of a multifunctional family. Trends Genet. 1993 Dec;9(12):427–433. doi: 10.1016/0168-9525(93)90106-r. [DOI] [PubMed] [Google Scholar]
  26. Gossen M., Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. doi: 10.1073/pnas.89.12.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Grimm S., Baeuerle P. A. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. Biochem J. 1993 Mar 1;290(Pt 2):297–308. doi: 10.1042/bj2900297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Hayashi T., Sekine T., Okamoto T. Identification of a new serine kinase that activates NF kappa B by direct phosphorylation. J Biol Chem. 1993 Dec 15;268(35):26790–26795. [PubMed] [Google Scholar]
  31. Herrmann C. P., Kraiss S., Montenarh M. Association of casein kinase II with immunopurified p53. Oncogene. 1991 May;6(5):877–884. [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. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Jelinek T., Weber M. J. Optimization of the resolution of phosphoamino acids by one-dimensional thin-layer electrophoresis. Biotechniques. 1993 Oct;15(4):628–630. [PubMed] [Google Scholar]
  36. Jin Y. J., Burakoff S. J. The 25-kDa FK506-binding protein is localized in the nucleus and associates with casein kinase II and nucleolin. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7769–7773. doi: 10.1073/pnas.90.16.7769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Jung M., Zhang Y., Lee S., Dritschilo A. Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Science. 1995 Jun 16;268(5217):1619–1621. doi: 10.1126/science.7777860. [DOI] [PubMed] [Google Scholar]
  38. Kamps M. P. Determination of phosphoamino acid composition by acid hydrolysis of protein blotted to Immobilon. Methods Enzymol. 1991;201:21–27. doi: 10.1016/0076-6879(91)01005-m. [DOI] [PubMed] [Google Scholar]
  39. Kerr L. D., Duckett C. S., Wamsley P., Zhang Q., Chiao P., Nabel G., McKeithan T. W., Baeuerle P. A., Verma I. M. The proto-oncogene bcl-3 encodes an I kappa B protein. Genes Dev. 1992 Dec;6(12A):2352–2363. doi: 10.1101/gad.6.12a.2352. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Krek W., Maridor G., Nigg E. A. Casein kinase II is a predominantly nuclear enzyme. J Cell Biol. 1992 Jan;116(1):43–55. doi: 10.1083/jcb.116.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kumar A., Haque J., Lacoste J., Hiscott J., Williams B. R. Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6288–6292. doi: 10.1073/pnas.91.14.6288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Kunsch C., Ruben S. M., Rosen C. A. Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation. Mol Cell Biol. 1992 Oct;12(10):4412–4421. doi: 10.1128/mcb.12.10.4412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Lin A., Frost J., Deng T., Smeal T., al-Alawi N., Kikkawa U., Hunter T., Brenner D., Karin M. Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell. 1992 Sep 4;70(5):777–789. doi: 10.1016/0092-8674(92)90311-y. [DOI] [PubMed] [Google Scholar]
  47. Lin R., Gewert D., Hiscott J. Differential transcriptional activation in vitro by NF-kappa B/Rel proteins. J Biol Chem. 1995 Feb 17;270(7):3123–3131. doi: 10.1074/jbc.270.7.3123. [DOI] [PubMed] [Google Scholar]
  48. Liou H. C., Baltimore D. Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system. Curr Opin Cell Biol. 1993 Jun;5(3):477–487. doi: 10.1016/0955-0674(93)90014-h. [DOI] [PubMed] [Google Scholar]
  49. Meisner H., Czech M. P. Phosphorylation of transcriptional factors and cell-cycle-dependent proteins by casein kinase II. Curr Opin Cell Biol. 1991 Jun;3(3):474–483. doi: 10.1016/0955-0674(91)90076-b. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Neri A., Chang C. C., Lombardi L., Salina M., Corradini P., Maiolo A. T., Chaganti R. S., Dalla-Favera R. B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. Cell. 1991 Dec 20;67(6):1075–1087. doi: 10.1016/0092-8674(91)90285-7. [DOI] [PubMed] [Google Scholar]
  52. Nolan G. P., Ghosh S., Liou H. C., Tempst P., Baltimore D. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. Cell. 1991 Mar 8;64(5):961–969. doi: 10.1016/0092-8674(91)90320-x. [DOI] [PubMed] [Google Scholar]
  53. Ostrowski J., Sims J. E., Sibley C. H., Valentine M. A., Dower S. K., Meier K. E., Bomsztyk K. A serine/threonine kinase activity is closely associated with a 65-kDa phosphoprotein specifically recognized by the kappa B enhancer element. J Biol Chem. 1991 Jul 5;266(19):12722–12733. [PubMed] [Google Scholar]
  54. Padmanabha R., Chen-Wu J. L., Hanna D. E., Glover C. V. Isolation, sequencing, and disruption of the yeast CKA2 gene: casein kinase II is essential for viability in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Aug;10(8):4089–4099. doi: 10.1128/mcb.10.8.4089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Pepin N., Roulston A., Lacoste J., Lin R., Hiscott J. Subcellular redistribution of HTLV-1 Tax protein by NF-kappa B/Rel transcription factors. Virology. 1994 Nov 1;204(2):706–716. doi: 10.1006/viro.1994.1586. [DOI] [PubMed] [Google Scholar]
  56. Pinna L. A. Casein kinase 2: an 'eminence grise' in cellular regulation? Biochim Biophys Acta. 1990 Sep 24;1054(3):267–284. doi: 10.1016/0167-4889(90)90098-x. [DOI] [PubMed] [Google Scholar]
  57. Rodriguez M. S., Michalopoulos I., Arenzana-Seisdedos F., Hay R. T. Inducible degradation of I kappa B alpha in vitro and in vivo requires the acidic C-terminal domain of the protein. Mol Cell Biol. 1995 May;15(5):2413–2419. doi: 10.1128/mcb.15.5.2413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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]
  59. Ruben S. M., Klement J. F., Coleman T. A., Maher M., Chen C. H., Rosen C. A. I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity. Genes Dev. 1992 May;6(5):745–760. doi: 10.1101/gad.6.5.745. [DOI] [PubMed] [Google Scholar]
  60. Ryseck R. P., Bull P., Takamiya M., Bours V., Siebenlist U., Dobrzanski P., Bravo R. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B. Mol Cell Biol. 1992 Feb;12(2):674–684. doi: 10.1128/mcb.12.2.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. 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]
  62. Schmid R. M., Perkins N. D., Duckett C. S., Andrews P. C., Nabel G. J. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. Nature. 1991 Aug 22;352(6337):733–736. doi: 10.1038/352733a0. [DOI] [PubMed] [Google Scholar]
  63. Seldin D. C., Leder P. Casein kinase II alpha transgene-induced murine lymphoma: relation to theileriosis in cattle. Science. 1995 Feb 10;267(5199):894–897. doi: 10.1126/science.7846532. [DOI] [PubMed] [Google Scholar]
  64. Shi Y., Brown E. D., Walsh C. T. Expression of recombinant human casein kinase II and recombinant heat shock protein 90 in Escherichia coli and characterization of their interactions. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2767–2771. doi: 10.1073/pnas.91.7.2767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science. 1987 Oct 30;238(4827):692–694. doi: 10.1126/science.3118464. [DOI] [PubMed] [Google Scholar]
  66. Sun S. C., Ganchi P. A., Ballard D. W., Greene W. C. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science. 1993 Mar 26;259(5103):1912–1915. doi: 10.1126/science.8096091. [DOI] [PubMed] [Google Scholar]
  67. Sun S. C., Ganchi P. A., Béraud C., Ballard D. W., Greene W. C. Autoregulation of the NF-kappa B transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1346–1350. doi: 10.1073/pnas.91.4.1346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Traenckner E. B., Wilk S., Baeuerle P. A. A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B. EMBO J. 1994 Nov 15;13(22):5433–5441. doi: 10.1002/j.1460-2075.1994.tb06878.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. 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]
  70. Yu I. J., Spector D. L., Bae Y. S., Marshak D. R. Immunocytochemical localization of casein kinase II during interphase and mitosis. J Cell Biol. 1991 Sep;114(6):1217–1232. doi: 10.1083/jcb.114.6.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]

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