The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors.
Genes & DevelopmentPublished 1 November 1993Open access
Amer A. Beg, A S Baldwin
Citations801
SJR quartileQ1
SJR score4.00
SNIP1.43
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
ScienceIκB: a Specific Inhibitor of the NF-κB Transcription Factor
2,181 Citations1988Patrick A. Baeuerle, David Baltimore
The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor in cells that do not express immunoglobulin kappa light chain genes.
NatureActivation in vitro of NF-κB" by phosphorylation of its inhibitor IκB"
1,192 Citations1990Sankar Ghosh, David Baltimore
An in vitro system in which addition of purified protein kinases to a partially purified NF-κB/IκB complex leads to the activation of the DNA-binding activity of NF-σB is used, which acts as a second messenger system, transducing activation signals from the cytoplasm to the nucleus.
CellActivation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor
1,189 Citations1988Patrick A. Baeuerle, D Baltimore
It is concluded that both 70Z/3 and HeLa cells contain apparently cytosolic NF-kappa B in a form with no evident DNA-binding activity, and phorbol esters both release the inhibition of binding and cause a translocation to the nucleus.
ScienceNF-κB Controls Expression of Inhibitor IκBα: Evidence for an Inducible Autoregulatory Pathway
1,112 Citations1993Shao‐Cong Sun, Parham A. Ganchi +2 more
Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B, and association of the newly synthesized I k Kappa B alpha with p65 restores intracellular inhibition of NF -kappaB DNA binding activity and prolongs the survival of this labile inhibitor.
NatureRapid proteolysis of IκB-α is necessary for activation of transcription factor NF-κB
1,110 Citations1993Thomas Henkel, Thomas Machleidt +4 more
It is reported that I kappa B-alpha (formerly MAD-3) is degraded in cells after stimulation with phorbol ester, interleukin-1, lipopolysaccharide and tumour necrosis factor-alpha, an event coincident with the appearance of active NF-kappa B.
International review of cytologyIMF-κB and Rel: Participants in a Multiform Transcriptional Regulatory System
936 Citations1993Mariagrazia Grilli, Jason J.-S. Chiu +1 more
This chapter highlights NF-кB/Rel protein complex, a family of dimer-forming proteins with homology to the rel oncogene that has the important ability to carry signals from the cytoplasm into the nucleus and trans -activate specific genes by binding directly to their promoters.
CellCharacterization of an immediate-early gene induced in adherent monocytes that encodes IκB-like activity
733 Citations1991Stephen Haskill, Amer A. Beg +7 more
The cloned MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation.
Genes & DevelopmentI kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention.
716 Citations1992Amer A. Beg, Steven M. Ruben +4 more
It is proposed that I kappa B/MAD-3 masks the NLSs of NF-kappa B and c-Rel and that this constitutes the mechanism for cytoplasmic retention of these proteins.
ScienceNF-kappa B activation by ultraviolet light not dependent on a nuclear signal
642 Citations1993Yoram Devary, Caridad Rosette +2 more
Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event, suggesting that the UV response does not require a signal generated in the nucleus and is likely to be initiated at or near the plasma membrane.
Proceedings of the National Academy of SciencesMutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.
625 Citations1993Keith Brown, Suncheol Park +3 more
It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate, cause rapid degradation of I kappa B-alpha, with concomitant activation of NF-kappa B, followed by a dramatic increase in I k Kappa B- alpha mRNA and protein synthesis.
NatureAnalysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins
527 Citations1990Samuel E. Lux, Kathryn M. John +1 more
Analysis of complementary DNA for human erythroid ankyrin indicates that the mature protein contains 1,880 amino acids comprising an N-terminal domain binding integral membrane proteins and tubulin, a central domain binding spectrin and vimentin, and an acidic C-Terminal 'regulatory' domain containing an alternatively spliced sequence missing from ankyrIn variant 2.2.
Genes & DevelopmentA 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB.
509 Citations1989Patrick A. Baeuerle, David Baltimore
Surprisingly, NF-kappaB could only be inactivated by I kappaB when p65 was bound, and it would appear that one function of p65 is to make NF-cappaB susceptible to inhibition by IKappaB.
CellThe oncoprotein Bcl-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers
502 Citations1993Vincent Bours
The data reveal a novel role for Bcl-3, distinct from that of the inhibitor I kappa B, and the results have implications for tumorigenesis.
CellThe candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control
458 Citations1990Hitoshi Ohno
Sequence analysis of the human bcl-3 gene predicts a protein containing seven tandem copies of the SWI6/cdc10 motif, which was previously identified in yeast genes that regulate events at the start of the cell cycle and in invertebrate transmembrane proteins involved in cell differentiation pathways.
CellPurified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNA
435 Citations1990Ulrike Zabel, Patrick A. Baeuerle
Two chromatographically distinct forms of I kappa B were purified and found to be more basic and 3-8 kd larger than the alpha form, which could explain how NF-kappa B can be activated in response to various agents that signal via different intracellular messenger systems.
Genes & DevelopmentThe candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers.
414 Citations1993Takashi Fujita, Garry P. Nolan +3 more
It is shown that in contrast to the inhibitory activity of I kappa B-alpha, the bcl-3 gene product superactivates NF-kappa B p50 homodimer-mediated gene expression both in vivo and in vitro.
CellThe precursor of NF-κB p50 has IκB-like functions
404 Citations1992Nancy R. Rice, Mary Lee MacKichan +1 more
CellB cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50
395 Citations1991Antonino Neri, Chih-Chao Chang +6 more
The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.
CellIntramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-κB subunit
388 Citations1992Thomas Henkel, Ulrike Zabel +4 more
It is shown that the non-DNA-binding precursor for the p50 subunit (p110), like NF-kappa B, is subject to control of nuclear uptake.
Genes & DevelopmentThe p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms.
356 Citations1993Martin Scott, Takashi Fujita +3 more
The EMBO JournalCytokine‐inducible expression in endothelial cells of an I kappa B alpha‐like gene is regulated by NF kappa B.
331 Citations1993Rainer de Martin, Bernard Vanhove +5 more
In porcine aortic endothelial cells, either IL‐1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which is referred to as ECI‐6 which could represent a novel feedback mechanism by which NFKappa B downregulates its own activity after transient activation of target genes has been achieved.
NatureThe candidate oncoprotein Bcl-3 is an antagonist of pSO/NF-κB-mediated inhibition
322 Citations1992Guido Franzoso, Vincent Bours +4 more
It is demonstrated that Bcl-3 can aid κB site-dependent transcription in vivo by counteracting the inhibitory effects of p50/NF-κB homodimers, and may therefore aid activation of select NF-κBs-regulated genes, including those of the human immunodeficiency virus.
The EMBO JournalNuclear uptake control of NF‐kappa B by MAD‐3, an I kappa B protein present in the nucleus.
319 Citations1993Ulrike Zabel, Thomas Henkel +2 more
It is shown here that the DNA‐binding p50 and p65 subunits of NF‐kappa B, as well as the I kappa B protein MAD‐3, all occur in the nucleus when overexpressed on their own.
ScienceNF-κB Subunit Regulation in Nontransformed CD4 <sup>+</sup> T Lymphocytes
318 Citations1992Sang‐Mo Kang, Annie-Chen Tran +2 more
Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-kappa B was studied in nontransformed CD4+ T lymphocyte clones and the switch from p50-p50 to p65-p65 complexes depended on a protein that caused sequestration of the p60- p50 complex in the nucleus.
Genes & Developmentp105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction.
283 Citations1993Frank Mercurio, Joseph A. DiDonato +2 more
It is demonstrated that the p105 and p98 precursors share functional properties with the I kappa B proteins, which also contain SWI6/ankyrin repeats, suggesting a second pathway leading to NF-kappa B induction, in which processing of the precursor rather than phosphorylation of I k Kappa B plays a major role.
CellIκBγ, a 70 kd protein identical to the C-terminal half of p110 NF-κB: A new member of the IκB family
271 Citations1992Jun‐ichiro Inoue, Lawrence D. Kerr +2 more
A cDNA corresponding to the 2.6 kb NF-κB mRNA species present in a variety of lymphoid cell lines has been molecularly cloned and the deduced 607 amino acid sequence is identical to the sequence of the C-terminal region of 110 kd NF-KKB protein, a new member of the IκB family of proteins and is referred to as IκBsγ.
Molecular Biology of the CellI 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.
269 Citations1992Parham A. Ganchi, Shenghuan Sun +2 more
The findings suggest that the nuclear localization signal and transactivation domain of NF-kappa B p65 constitute a bipartite system that is critically involved in the inhibitory function of I kappa B/MAD-3.
CellThe polarity of the dorsoventral axis in the drosophila embryo is defined by an extracellular signal
264 Citations1991David A. Stein, Siegfried Roth +2 more
It is proposed that the polarizing activity, normally present at the ventral side of the egg, is a ligand for the Toll receptor, and local activation of the Toll protein by the ligand initiates the formation of the nuclear concentration gradient of the dorsal protein, thereby determining dorsoventral pattern.
The EMBO JournalThe characterization of the promoter of the gene encoding the p50 subunit of NF‐kappa B indicates that it participates in its own regulation.
249 Citations1992Rosa Ten, C. V. Paya +6 more
The involvement of NF‐kappa B in the regulation of the p50 gene is supported by the inhibition of the PMA activation of the promoter by an NF‐ kappa B transdominant negative mutant, as well as the product of the v‐rel oncogene.
Cellcactus, a gene involved in dorsoventral pattern formation of Drosophila, is related to the IκB gene family of vertebrates
246 Citations1992Robert Geisler, Andreas Bergmann +2 more
B bacterially expressed cactus protein can inhibit DNA binding of dorsal protein in vitro and has similarity to the I kappa B proteins that inhibit the vertebrate transcription factor NF-kappa B.
NatureCandidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-κB
246 Citations1992F. Gregory Wulczyn, Michael Naumann +1 more
It is shown that the proto-oncogene bcl-3, believed to be involved in certain human B-cell leukaemias17, encodes a protein that functions as an IκB-like molecule for native NF-κB but is specific for the p50 subunit.
ScienceRel-Associated pp40: an Inhibitor of the Rel Family of Transcription Factors
239 Citations1991Nathan Davis, Sankar Ghosh +5 more
The results suggest that rel-related transcription factors, which are capable of cytosolic to nuclear translocation, may be held in the cytosol by interaction with related cytoplasmic anchor molecules.
Proceedings of the National Academy of SciencesThe 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.
234 Citations1992Eunice N. Hatada, Alexandra Nieters +6 more
It is shown that the C-terminal half of p105, when expressed as a separate molecule, binds to p50 and can rapidly disrupt protein-DNA complexes of p50 or native NF-kappa B and strongly suggest that the ankyrin repeats in these factors are involved in protein-protein interactions with the rel-like domain of p 50.
CellCharacterization of the Drosophila cactus locus and analysis of interactions between cactus and dorsal proteins
229 Citations1992Simon Kidd
It is shown that the cactus locus produces two proteins that differ at their carboxy termini; both contain six cdc 10/SWI6 repeats that are sufficient for binding to dorsal and for inhibiting the ability of dorsal to bind DNA.
Journal of Biological ChemistryLipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells
227 Citations1993Susan R. Cordle, Ruth M. Donald +2 more
It is shown that LPS induces nuclear expression of c-Rel/p50 heterodimers as well as p50/p65 (NF-kappa B) kappa B DNA-binding complexes in human monocytic THP-1 cells and induces phosphorylated MAD3.
Cellpelle encodes a protein kinase required to establish dorsoventral polarity in the Drosophila embryo
212 Citations1993Christopher A. Shelton, Steven A. Wasserman
The pelle gene is required for the nuclear import of dorsal protein that establishes dorsoventral polarity in Drosophila embryos and genetic mapping and molecular characterization provide direct evidence for the role of phosphorylation in the in vivo regulation of a rel-like transcription factor.
Genes & DevelopmentThe rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation.
205 Citations1991Lawrence D. Kerr, Jun‐ichiro Inoue +5 more
It is demonstrated that purified pp40 not only inhibits the binding of Rel, but also NF-kappa B (p50-p65) heterocomplex to DNA, and labeled I kappa B beta can be immunoprecipitated with pp40 antibodies.
Journal of Biological ChemistryKappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1.
185 Citations1993Timothy S. Finco, Albert S. Baldwin
It is demonstrated that expression of activated forms of the GTP-binding protein Ras or of the serine/threonine kinase Raf-1 results in the activation of transcription specifically through kappa B sites, illuminating a signal transduction pathway in which NF-kappa B/Rel family members participate and also implicate a pathway responsible for kappaB site-dependent gene expression during cell growth and in immune and inflammatory responses.
Current Opinion in Genetics & DevelopmentThe inhibitory ankyrin and activator Rel proteins
183 Citations1992Garry P. Nolan, David Baltimore
NatureProcessing of the precursor of NF-κB by the HIV-1 protease during acute infection
174 Citations1991Yves Rivière, Volker Blank +2 more
It is shown here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex, which is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex.
The EMBO JournalThe NF‐kappa B p50 precursor, p105, contains an internal I kappa B‐like inhibitor that preferentially inhibits p50.
171 Citations1992Hsiou‐Chi Liou, Garry P. Nolan +3 more
It is shown that the bacterially expressed and purified carboxy‐terminal region (CTR) of p105 abolishes the binding of p50 homodimers to a kappa B motif but minimally affects thebinding of p65 homodIMers and NF‐kappa B.
The EMBO JournalThe 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.
148 Citations1993Michael Naumann, F. Gregory Wulczyn +1 more
A function of p105 as a cytoplasmic assembly unit for homo‐ and heteromeric NF‐kappa B complexes and of Bcl‐3 as an I kappa B with novel subunit specificity are discussed.
Proceedings of the National Academy of SciencesDirect 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.
137 Citations1992Jun‐ichiro Inoue, Lawrence D. Kerr +4 more
It is proposed that the ankyrin repeats and the C-terminal region of pp40 form a structure that associates with the rel homology domain to inhibit DNA binding activity.
Genes & DevelopmentThe proto-oncogene bcl-3 encodes an I kappa B protein.
118 Citations1992Lawrence D. Kerr, Colin S. Duckett +7 more
It is proposed that the bcl-3 and 37-kD (I kappa B alpha) proteins are related and are members of the I kappaB family.
The Journal of ImmunologyPromoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL
102 Citations1993Patricia C. Cogswell, Robert I. Scheinman +1 more
The data demonstrate that the p50/p105 NF-kappa B gene is regulated by members of the NF- kappa B/Rel family and likely by other important transcription factors.
Genes & DevelopmentSelective nuclear transport of the Drosophila morphogen dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A.
86 Citations1992Jacqueline L. Norris, James L. Manley
Evidence is presented that the signaling pathway from Toll to dl involves protein kinase A (PKA) and that nuclear transport and activation of dl results from phosphorylation ofdl by PKA and the significance of these results with respect to Drosophila embryogenesis and to the regulation of the mammalian transcription factor NF-kappa B.
The EMBO JournalCommon structural constituents confer I kappa B activity to NF‐kappa B p105 and I kappa B/MAD‐3.
86 Citations1993Eunice N. Hatada, Michael Naumann +1 more
It is demonstrated that deletion of only three amino acids in the first repeat converts the subunit specificity of the p105 ARD into that of MAD‐3/I kappa B, and functionally the ARD in these molecules has a modular structure.