Home LiteratureArticle Details
PMID: 7925301 Published · ppublish English Journal Article

Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha determine pools of constitutive and inducible NF-kappa B activity.

The EMBO journal ·Vol. 13 ·No. 19 ·1994-10-03 ·Pages 4608-16

Dobrzanski P, Ryseck RP, Bravo R

Abstract

The Rel-NF-kappa B family of transcription factors plays a crucial role in the regulation of genes involved in inflammatory and immune responses. We demonstrate that in vivo, in contrast to the other members of the family, RelB associates efficiently only with NF-kappa B1 (p105-p50) and NF-kappa B2 (p100-p52), but not with cRel or p65. The RelB-p52 heterodimers display a much lower affinity for I kappa B alpha than RelB-p50 heterodimers or p65 complexes. However, similarly to the other Rel-NF-kappa B complexes, RelB-p52 can upregulate the synthesis of I kappa B alpha leading to the cytoplasmic trapping of dimers which have a higher affinity for the inhibitor. We suggest that a hierarchy of interactions between I kappa B alpha and the different Rel-NF-kappa B complexes governs their cellular distribution. This results in the presence of two distinct pools of NF-kappa B activity which differ in their composition: one a constitutive nuclear and the other an inducible cytoplasmic activity.

MeSH Terms
B-Lymphocytes/metabolism Biopolymers Cell Line DNA-Binding Proteins/biosynthesis,metabolism,physiology Gene Expression Regulation/physiology Humans I-kappa B Proteins NF-KappaB Inhibitor alpha NF-kappa B/metabolism,physiology Protein Binding Proto-Oncogene Proteins Transcription Factor RelB Transcription Factors/metabolism,physiology
Chemicals
Biopolymers DNA-Binding Proteins I-kappa B Proteins NF-kappa B NFKBIA protein, human Proto-Oncogene Proteins RELB protein, human Transcription Factors NF-KappaB Inhibitor alpha Transcription Factor RelB
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dobrzanski P
Department of Molecular Biology, Bristol-Myers-Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Ryseck R P
Bravo R
References (62)
62 references, click to expand
  1. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  2. Evidence for differential functions of the p50 and p65 subunits of NF-kappa B with a cell adhesion model.
    Mol Cell Biol. 1993 Jun;13(6):3802-10 PMID: 8497281
  3. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  4. Molecular and biochemical characterization of the human trk proto-oncogene.
    Mol Cell Biol. 1989 Jan;9(1):24-33 PMID: 2927393
  5. Nuclear receptors enhance our understanding of transcription regulation.
    Trends Genet. 1988 Nov;4(11):309-14 PMID: 2853466
  6. The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control.
    Cell. 1990 Mar 23;60(6):991-7 PMID: 2180580
  7. 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):1007-18 PMID: 2203531
  8. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function.
    Cell. 1990 Nov 16;63(4):803-14 PMID: 2225078
  9. Expression of different Jun and Fos proteins during the G0-to-G1 transition in mouse fibroblasts: in vitro and in vivo associations.
    Mol Cell Biol. 1991 May;11(5):2451-9 PMID: 1901942
  10. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits.
    Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 PMID: 2018779
  11. 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):1464-76 PMID: 1907941
  12. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65.
    Nature. 1991 Aug 22;352(6337):733-6 PMID: 1876189
  13. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B.
    Mol Cell Biol. 1992 Feb;12(2):674-84 PMID: 1732739
  14. A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene.
    EMBO J. 1992 Jan;11(1):205-13 PMID: 1740106
  15. The c-rel protooncogene product c-Rel but not NF-kappa B binds to the intronic region of the human interferon-gamma gene at a site related to an interferon-stimulable response element.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1740-4 PMID: 1542667
  16. I kappa B gamma, a 70 kd protein identical to the C-terminal half of p110 NF-kappa B: a new member of the I kappa B family.
    Cell. 1992 Mar 20;68(6):1109-20 PMID: 1339305
  17. 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):1736-46 PMID: 1372388
  18. The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding.
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2489-93 PMID: 1532257
  19. Transcriptional regulation of the HIV-1 promoter by NF-kappa B in vitro.
    Genes Dev. 1992 May;6(5):761-74 PMID: 1577271
  20. Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B.
    Genes Dev. 1992 May;6(5):775-87 PMID: 1577272
  21. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats.
    Trends Biochem Sci. 1992 Apr;17(4):135-40 PMID: 1533967
  22. Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex.
    Mol Cell Biol. 1992 Jun;12(6):2898-908 PMID: 1588976
  23. The inhibitory ankyrin and activator Rel proteins.
    Curr Opin Genet Dev. 1992 Apr;2(2):211-20 PMID: 1386268
  24. The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50.
    EMBO J. 1992 Aug;11(8):3003-9 PMID: 1639070
  25. The regulation of transcription by phosphorylation.
    Cell. 1992 Aug 7;70(3):375-87 PMID: 1643656
  26. 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):4067-75 PMID: 1508203
  27. The Rel family: models for transcriptional regulation and oncogenic transformation.
    Biochim Biophys Acta. 1992 Sep 14;1114(1):1-17 PMID: 1327144
  28. 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):4412-21 PMID: 1406630
  29. 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):11803-10 PMID: 8505309
  30. The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms.
    Genes Dev. 1993 Jul;7(7A):1266-76 PMID: 8319912
  31. Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B.
    EMBO J. 1993 Jul;12(7):2773-9 PMID: 8334993
  32. A dominant negative protein kinase C zeta subspecies blocks NF-kappa B activation.
    Mol Cell Biol. 1993 Aug;13(8):4770-5 PMID: 8336714
  33. 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):17676-9 PMID: 8349650
  34. Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system.
    Curr Opin Cell Biol. 1993 Jun;5(3):477-87 PMID: 8352966
  35. NF-kappa B activation by ultraviolet light not dependent on a nuclear signal.
    Science. 1993 Sep 10;261(5127):1442-5 PMID: 8367725
  36. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B.
    Nature. 1993 Sep 9;365(6442):182-5 PMID: 8371761
  37. NF-kappa B p100 (Lyt-10) is a component of H2TF1 and can function as an I kappa B-like molecule.
    Mol Cell Biol. 1993 Oct;13(10):6089-101 PMID: 8413211
  38. NF-kappa B subunit-specific regulation of the interleukin-8 promoter.
    Mol Cell Biol. 1993 Oct;13(10):6137-46 PMID: 8413215
  39. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.
    Mol Cell Biol. 1993 Oct;13(10):6283-9 PMID: 7692229
  40. Distinct NF-kappa B/Rel transcription factors are responsible for tissue-specific and inducible gene activation.
    Nature. 1993 Oct 21;365(6448):767-70 PMID: 7692309
  41. In vivo control of NF-kappa B activation by I kappa B alpha.
    EMBO J. 1993 Dec;12(12):4685-95 PMID: 8223478
  42. The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors.
    Genes Dev. 1993 Nov;7(11):2064-70 PMID: 8224838
  43. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells.
    Development. 1993 Aug;118(4):1221-31 PMID: 8269849
  44. Autoregulation of I kappa B alpha activity.
    Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):28-32 PMID: 8278379
  45. 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):1346-50 PMID: 8108414
  46. Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B.
    EMBO J. 1994 Feb 15;13(4):861-70 PMID: 8112299
  47. The I kappa B proteins: members of a multifunctional family.
    Trends Genet. 1993 Dec;9(12):427-33 PMID: 8122310
  48. Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription.
    Mol Cell Biol. 1994 Apr;14(4):2593-603 PMID: 8139561
  49. The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B-mediated inhibition.
    Nature. 1992 Sep 24;359(6393):339-42 PMID: 1406939
  50. The precursor of NF-kappa B p50 has I kappa B-like functions.
    Cell. 1992 Oct 16;71(2):243-53 PMID: 1423592
  51. Role of rel family genes in normal and malignant lymphoid cell growth.
    Cancer Surv. 1992;15:69-87 PMID: 1451115
  52. I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding.
    Mol Biol Cell. 1992 Dec;3(12):1339-52 PMID: 1493333
  53. The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B.
    EMBO J. 1993 Jan;12(1):213-22 PMID: 8428580
  54. 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. 1993 Mar;13(3):1572-82 PMID: 8441398
  55. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system.
    Int Rev Cytol. 1993;143:1-62 PMID: 8449662
  56. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits.
    Biochem J. 1993 Mar 1;290 ( Pt 2):297-308 PMID: 8452515
  57. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway.
    Science. 1993 Mar 26;259(5103):1912-5 PMID: 8096091
  58. p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction.
    Genes Dev. 1993 Apr;7(4):705-18 PMID: 8458581
  59. 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):2532-6 PMID: 8460169
  60. 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):3301-10 PMID: 8497253
  61. The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner.
    Mol Cell Biol. 1993 Jun;13(6):3557-66 PMID: 8497270
  62. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3365-9 PMID: 2437578
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-10-03
Pages
4608-16
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395393
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2