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Transcription factor PDB id
1ikn
Jmol
Contents
Protein chains
283 a.a. *
113 a.a. *
216 a.a. *
Waters ×212
* Residue conservation analysis
PDB id:
1ikn
Name: Transcription factor
Title: Ikappabalpha/nf-kappab complex
Structure: Protein (nf-kappa-b p65 subunit). Chain: a. Fragment: n-terminal and dimerization domains. Synonym: p65. Engineered: yes. Protein (nf-kappa-b p50d subunit). Chain: c. Fragment: n-terminal and dimerization domains. Synonym: p50d.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: mad-3.
Biol. unit: Trimer (from PQS)
Resolution:
2.30Å     R-factor:   0.223     R-free:   0.277
Authors: T.Huxford,D.-B.Huang,S.Malek,G.Ghosh
Key ref:
T.Huxford et al. (1998). The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation. Cell, 95, 759-770. PubMed id: 9865694 DOI: 10.1016/S0092-8674(00)81699-2
Date:
13-Nov-98     Release date:   12-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
Seq:
Struc: 		 
Seq:
Struc: 		549 a.a.
283 a.a.
Protein chain
Pfam   ArchSchema ?
P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit
Seq:
Struc: 		 
Seq:
Struc: 		971 a.a.
113 a.a.
Protein chain
Pfam   ArchSchema ?
P25963  (IKBA_HUMAN) -  NF-kappa-B inhibitor alpha
Seq:
Struc: 		317 a.a.
216 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription   2 terms 
  Biochemical function     transcription factor activity     1 term  

 

 
DOI no: 10.1016/S0092-8674(00)81699-2 Cell 95:759-770 (1998)
PubMed id: 9865694  
 
 
The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation.
T.Huxford, D.B.Huang, S.Malek, G.Ghosh.
 
  ABSTRACT  
 
IkappaBalpha regulates the transcription factor NF-kappaB through the formation of stable IkappaBalpha/NF-kappaB complexes. Prior to induction, IkappaBalpha retains NF-kappaB in the cytoplasm until the NF-kappaB activation signal is received. After activation, NF-kappaB is removed from gene promoters through association with nuclear IkappaBalpha, restoring the preinduction state. The 2.3 A crystal structure of IkappaBalpha in complex with the NF-kappaB p50/p65 heterodimer reveals mechanisms of these inhibitory activities. The presence of IkappaBalpha allows large en bloc movement of the NF-kappaB p65 subunit amino-terminal domain. This conformational change induces allosteric inhibition of NF-kappaB DNA binding. Amino acid residues immediately preceding the nuclear localization signals of both NF-kappaB p50 and p65 subunits are tethered to the IkappaBalpha amino-terminal ankyrin repeats, impeding NF-kappaB from nuclear import machinery recognition.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. NF-κB p50/p65 Heterodimer in Its Open and Closed Conformations(a) NF-κB p50/p65 heterodimer bound to κB DNA target ([16]) exhibits its open conformation. Note that the amino-terminal domain of p50 subunit is present in this DNA-bound complex.(b) Stereoview of the p50/p65 heterodimer in its DNA-bound open conformation (p50dd in blue, p50 amino-terminal domain not present, and p65RHR in cyan) and IκBα-bound closed conformation (p50dd in green and p65RHR in red) overlayed by superposition of the dimerization domains. The p65 amino-terminal domain rotates 171° and translates 38 Å between the two conformations. 		Figure 5.
Figure 5. IκBα Interactions with the p65 Amino-Terminal Domain and NLS Polypeptides(a) Residues from the sixth ankyrin repeat of IκBα (in purple) contact side chains from the p65 amino-terminal domain (in red). Amino acid single letter codes are used.(b) The interaction of the p65 NLS polypeptide (skeleton) is shown with IκBα ankyrin repeats 1, 2, and 3 depicted as a molecular surface. The orientation is the same as in Figure 2A.(c) Molecular surface representation of the p65 amino-terminal domain according to local electrostatic surface potentials (blue, positive; red, negative). Skeleton representation of the amino acids 268–288 (part of sixth ankyrin repeat and PEST sequence) of IκBα contact the basic patch (blue) of the p65 amino-terminal domain. Orientation is as in Figure 2B. DNA-binding loops 2 and 3 are labeled L2 and L3, respectively. This is only part of the extensive network of interacting electrostatic surfaces formed between the amino-terminal and dimerization domains of p65 and IκBα.
 
  The above figures are reprinted by permission from Cell Press: Cell (1998, 95, 759-770) copyright 1998.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472811 B.Manavalan, R.Govindaraj, G.Lee, and S.Choi (2011).
Molecular modeling-based evaluation of dual function of IκBζ ankyrin repeat domain in toll-like receptor signaling.
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21135870 C.Zheng, Q.Yin, and H.Wu (2011).
Structural studies of NF-κB signaling.
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21329696 I.DeVries, D.U.Ferreiro, I.E.Sánchez, and E.A.Komives (2011).
Folding kinetics of the cooperatively folded subdomain of the IκBα ankyrin repeat domain.
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20890592 K.Y.Moon (2011).
Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.
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21264230 L.Chen, Q.Meng, W.Kao, and Y.Xia (2011).
IκB Kinase β Regulates Epithelium Migration during Corneal Wound Healing.
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21401918 L.Gu, T.Tsuji, M.A.Jarboui, G.P.Yeo, N.Sheehy, W.W.Hall, and V.W.Gautier (2011).
Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
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21220295 S.C.Sue, V.Alverdi, E.A.Komives, and H.J.Dyson (2011).
Detection of a ternary complex of NF-kappaB and IkappaBalpha with DNA provides insights into how IkappaBalpha removes NF-kappaB from transcription sites.
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21333553 S.M.Wuerzberger-Davis, Y.Chen, D.T.Yang, J.D.Kearns, P.W.Bates, C.Lynch, N.C.Ladell, M.Yu, A.Podd, H.Zeng, T.T.Huang, R.Wen, A.Hoffmann, D.Wang, and S.Miyamoto (2011).
Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation.
  Immunity, 34, 188-200.  
21187855 S.Miyamoto (2011).
Nuclear initiated NF-κB signaling: NEMO and ATM take center stage.
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21158742 T.Valovka, and M.O.Hottiger (2011).
p65 controls NF-κB activity by regulating cellular localization of IκBβ.
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21203422 B.Manavalan, S.Basith, Y.M.Choi, G.Lee, and S.Choi (2010).
Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis.
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20055496 D.U.Ferreiro, and E.A.Komives (2010).
Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha.
  Biochemistry, 49, 1560-1567.  
20191354 K.Y.Moon (2010).
N-nitroso-N-methylurea and N-nitroso-N-ethylurea induce upregulation of cellular NF-kappa B activity through protein kinase C-dependent pathway in human malignant keratinocytes.
  Arch Pharm Res, 33, 133-139.  
20056148 M.Rusu, and S.Birmanns (2010).
Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions.
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19453763 A.Fath-Goodin, J.A.Kroemer, and B.A.Webb (2009).
The Campoletis sonorensis ichnovirus vankyrin protein P-vank-1 inhibits apoptosis in insect Sf9 cells.
  Insect Mol Biol, 18, 497-506.  
19507254 A.Lake, L.A.Shield, P.Cordano, D.T.Chui, J.Osborne, S.Crae, K.S.Wilson, S.Tosi, S.J.Knight, S.Gesk, R.Siebert, R.T.Hay, and R.F.Jarrett (2009).
Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases.
  Int J Cancer, 125, 1334-1342.  
  20066092 A.Oeckinghaus, and S.Ghosh (2009).
The NF-kappaB family of transcription factors and its regulation.
  Cold Spring Harbor Perspect Biol, 1, a000034.  
19524307 B.A.Jordan, and M.R.Kreutz (2009).
Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling.
  Trends Neurosci, 32, 392-401.  
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Functional dynamics of the folded ankyrin repeats of I kappa B alpha revealed by nuclear magnetic resonance.
  Biochemistry, 48, 8023-8031.  
19224334 C.F.László, and S.Wu (2009).
Old target new approach: an alternate NF-kappaB activation pathway via translation inhibition.
  Mol Cell Biochem, 328, 9.  
  20066093 F.Wan, and M.J.Lenardo (2009).
Specification of DNA binding activity of NF-kappaB proteins.
  Cold Spring Harbor Perspect Biol, 1, a000067.  
19683540 J.C.Stroud, A.Oltman, A.Han, D.L.Bates, and L.Chen (2009).
Structural basis of HIV-1 activation by NF-kappaB--a higher-order complex of p50:RelA bound to the HIV-1 LTR.
  J Mol Biol, 393, 98.
PDB code: 3gut
19056378 J.Shant, K.Cheng, B.S.Marasa, J.Y.Wang, and J.P.Raufman (2009).
Akt-dependent NF-kappaB activation is required for bile acids to rescue colon cancer cells from stress-induced apoptosis.
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19187222 L.Liu, T.Sakai, N.H.Tran, R.Mukai-Sakai, R.Kaji, and K.Fukui (2009).
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MUC1-C oncoprotein functions as a direct activator of the nuclear factor-kappaB p65 transcription factor.
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19887633 S.Bergqvist, V.Alverdi, B.Mengel, A.Hoffmann, G.Ghosh, and E.A.Komives (2009).
Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha.
  Proc Natl Acad Sci U S A, 106, 19328-19333.  
19327364 S.C.Sue, and H.J.Dyson (2009).
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19617375 S.Maas, and W.M.Gommans (2009).
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  Nucleic Acids Res, 37, 5822-5829.  
  20066103 T.Huxford, and G.Ghosh (2009).
A structural guide to proteins of the NF-kappaB signaling module.
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19668332 V.Ropars, G.Despouy, M.H.Stern, S.Benichou, C.Roumestand, and S.T.Arold (2009).
The TCL1A oncoprotein interacts directly with the NF-kappaB inhibitor IkappaB.
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19117955 Y.Yang, X.Wang, C.A.Hawkins, K.Chen, J.Vaynberg, X.Mao, Y.Tu, X.Zuo, J.Wang, Y.X.Wang, C.Wu, N.Tjandra, and J.Qin (2009).
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18203717 B.L.Moss, S.Gross, S.T.Gammon, A.Vinjamoori, and D.Piwnica-Worms (2008).
Identification of a ligand-induced transient refractory period in nuclear factor-kappaB signaling.
  J Biol Chem, 283, 8687-8698.  
18401342 E.Mathes, E.L.O'Dea, A.Hoffmann, and G.Ghosh (2008).
NF-kappaB dictates the degradation pathway of IkappaBalpha.
  EMBO J, 27, 1357-1367.  
18308615 J.A.Schmid, and A.Birbach (2008).
IkappaB kinase beta (IKKbeta/IKK2/IKBKB)--a key molecule in signaling to the transcription factor NF-kappaB.
  Cytokine Growth Factor Rev, 19, 157-165.  
18545105 M.D.Buzzelli, M.Navaratnarajah, T.Ahmed, M.Nagarajan, M.L.Shumate, C.H.Lang, and R.N.Cooney (2008).
Nuclear factor kappaB mediates the inhibitory effects of interleukin-1 on growth hormone-inducible gene expression.
  J Trauma, 64, 1427.  
18515839 M.Gao, and J.Skolnick (2008).
DBD-Hunter: a knowledge-based method for the prediction of DNA-protein interactions.
  Nucleic Acids Res, 36, 3978-3992.  
18299349 N.Bakkar, J.Wang, K.J.Ladner, H.Wang, J.M.Dahlman, M.Carathers, S.Acharyya, M.A.Rudnicki, A.D.Hollenbach, and D.C.Guttridge (2008).
IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis.
  J Cell Biol, 180, 787-802.  
18451141 R.S.Huang, S.Duan, E.O.Kistner, W.K.Bleibel, S.M.Delaney, D.L.Fackenthal, S.Das, and M.E.Dolan (2008).
Genetic variants contributing to daunorubicin-induced cytotoxicity.
  Cancer Res, 68, 3161-3168.  
18515173 S.Basak, and A.Hoffmann (2008).
Crosstalk via the NF-kappaB signaling system.
  Cytokine Growth Factor Rev, 19, 187-197.  
18824506 S.Bergqvist, G.Ghosh, and E.A.Komives (2008).
The IkappaBalpha/NF-kappaB complex has two hot spots, one at either end of the interface.
  Protein Sci, 17, 2051-2058.  
18565540 S.C.Sue, C.Cervantes, E.A.Komives, and H.J.Dyson (2008).
Transfer of flexibility between ankyrin repeats in IkappaB* upon formation of the NF-kappaB complex.
  J Mol Biol, 380, 917-931.  
18511071 S.M.Truhlar, E.Mathes, C.F.Cervantes, G.Ghosh, and E.A.Komives (2008).
Pre-folding IkappaBalpha alters control of NF-kappaB signaling.
  J Mol Biol, 380, 67-82.  
18849440 S.R.White, B.M.Fischer, B.A.Marroquin, and R.Stern (2008).
Interleukin-1beta mediates human airway epithelial cell migration via NF-kappaB.
  Am J Physiol Lung Cell Mol Physiol, 295, L1018-L1027.  
18034829 T.Shin, S.Kuboki, and A.B.Lentsch (2008).
Roles of nuclear factor-kappaB in postischemic liver.
  Hepatol Res, 38, 429-440.  
18988733 W.H.Yang, S.Y.Park, H.W.Nam, d.o. .H.Kim, J.G.Kang, E.S.Kang, Y.S.Kim, H.C.Lee, K.S.Kim, and J.W.Cho (2008).
NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions.
  Proc Natl Acad Sci U S A, 105, 17345-17350.  
17174335 D.U.Ferreiro, C.F.Cervantes, S.M.Truhlar, S.S.Cho, P.G.Wolynes, and E.A.Komives (2007).
Stabilizing IkappaBalpha by "consensus" design.
  J Mol Biol, 365, 1201-1216.  
17171436 F.Wang, J.Hu, P.Song, and W.Gong (2007).
Two novel transcripts encoding two Ankyrin repeat containing proteins have preponderant expression during the mouse spermatogenesis.
  Mol Biol Rep, 34, 249-260.  
17991436 K.Hochrainer, G.Racchumi, and J.Anrather (2007).
Hypo-phosphorylation leads to nuclear retention of NF-kappaB p65 due to impaired IkappaBalpha gene synthesis.
  FEBS Lett, 581, 5493-5499.  
18048681 L.J.Terry, E.B.Shows, and S.R.Wente (2007).
Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport.
  Science, 318, 1412-1416.  
17097678 M.Sommerhalter, Y.Zhang, and A.C.Rosenzweig (2007).
Solution structure of the COMMD1 N-terminal domain.
  J Mol Biol, 365, 715-721.
PDB code: 2h2m
17421103 M.W.Quasney (2007).
Genetic influences on severe lung injury: how many more genes?
  Crit Care Med, 35, 976-977.  
17881247 N.Rouas-Freiss, P.Moreau, C.Menier, J.LeMaoult, and E.D.Carosella (2007).
Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses.
  Semin Cancer Biol, 17, 413-421.  
17235259 R.Zhai, W.Zhou, M.N.Gong, B.T.Thompson, L.Su, C.Yu, P.Kraft, and D.C.Christiani (2007).
Inhibitor kappaB-alpha haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians.
  Crit Care Med, 35, 893-898.  
17910475 V.A.Yakovlev, I.J.Barani, C.S.Rabender, S.M.Black, J.K.Leach, P.R.Graves, G.E.Kellogg, and R.B.Mikkelsen (2007).
Tyrosine nitration of IkappaBalpha: a novel mechanism for NF-kappaB activation.
  Biochemistry, 46, 11671-11683.  
18040287 Y.Chen, H.H.Li, J.Fu, X.F.Wang, Y.B.Ren, L.W.Dong, S.H.Tang, S.Q.Liu, M.C.Wu, and H.Y.Wang (2007).
Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.
  Cell Res, 17, 1020-1029.  
17607554 Z.H.Wu, and S.Miyamoto (2007).
Many faces of NF-kappaB signaling induced by genotoxic stress.
  J Mol Med, 85, 1187-1202.  
17054552 A.A.Khalil, J.C.Hall, F.A.Aziz, and P.Price (2006).
Tumour necrosis factor: implications for surgical patients.
  ANZ J Surg, 76, 1010-1016.  
16733806 G.Calvaruso, M.Giuliano, P.Portanova, A.De Blasio, R.Vento, and G.Tesoriere (2006).
Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8.
  Mol Cell Biochem, 287, 13-19.  
16530045 J.J.Wilson, and R.A.Kovall (2006).
Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.
  Cell, 124, 985-996.
PDB code: 2fo1
16467110 J.Yang, K.I.Amiri, J.R.Burke, J.A.Schmid, and A.Richmond (2006).
BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways.
  Clin Cancer Res, 12, 950-960.  
16760470 M.J.Schaaf, L.Willetts, B.P.Hayes, B.Maschera, E.Stylianou, and S.N.Farrow (2006).
The relationship between intranuclear mobility of the NF-kappaB subunit p65 and its DNA binding affinity.
  J Biol Chem, 281, 22409-22420.  
16756995 S.Bergqvist, C.H.Croy, M.Kjaergaard, T.Huxford, G.Ghosh, and E.A.Komives (2006).
Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex.
  J Mol Biol, 360, 421-434.  
16934999 S.M.Truhlar, C.H.Croy, J.W.Torpey, J.R.Koeppe, and E.A.Komives (2006).
Solvent accessibility of protein surfaces by amide H/2H exchange MALDI-TOF mass spectrometry.
  J Am Soc Mass Spectrom, 17, 1490-1497.  
17148610 S.M.Truhlar, J.W.Torpey, and E.A.Komives (2006).
Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB.DNA interaction fold upon binding to NF-kappaB.
  Proc Natl Acad Sci U S A, 103, 18951-18956.  
16530044 Y.Nam, P.Sliz, L.Song, J.C.Aster, and S.C.Blacklow (2006).
Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes.
  Cell, 124, 973-983.
PDB codes: 2f8x 2f8y
17049124 Z.P.Wang, S.X.Cai, D.B.Liu, X.Xu, and H.P.Liang (2006).
Anti-inflammatory effects of a novel peptide designed to bind with NF-kappaB p50 subunit.
  Acta Pharmacol Sin, 27, 1474-1478.  
15923614 E.Hertlein, J.Wang, K.J.Ladner, N.Bakkar, and D.C.Guttridge (2005).
RelA/p65 regulation of IkappaBbeta.
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15485830 G.Qing, Z.Qu, and G.Xiao (2005).
Regulation of NF-kappa B2 p100 processing by its cis-acting domain.
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16061795 H.Thoetkiattikul, M.H.Beck, and M.R.Strand (2005).
Inhibitor kappaB-like proteins from a polydnavirus inhibit NF-kappaB activation and suppress the insect immune response.
  Proc Natl Acad Sci U S A, 102, 11426-11431.  
15919914 J.A.Kroemer, and B.A.Webb (2005).
Ikappabeta-related vankyrin genes in the Campoletis sonorensis ichnovirus: temporal and tissue-specific patterns of expression in parasitized Heliothis virescens lepidopteran hosts.
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16302975 J.J.Babon, S.Yao, D.P.DeSouza, C.F.Harrison, L.J.Fabri, E.Liepinsh, S.D.Scrofani, M.Baca, and R.S.Norton (2005).
Secondary structure assignment of mouse SOCS3 by NMR defines the domain boundaries and identifies an unstructured insertion in the SH2 domain.
  FEBS J, 272, 6120-6130.  
15858823 J.Osborne, A.Lake, F.E.Alexander, G.M.Taylor, and R.F.Jarrett (2005).
Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma.
  Int J Cancer, 116, 646-651.  
16244662 L.Opperman, B.Hook, M.DeFino, D.S.Bernstein, and M.Wickens (2005).
A single spacer nucleotide determines the specificities of two mRNA regulatory proteins.
  Nat Struct Mol Biol, 12, 945-951.  
15757897 M.P.Lussier, S.Cayouette, P.K.Lepage, C.L.Bernier, N.Francoeur, M.St-Hilaire, M.Pinard, and G.Boulay (2005).
MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC.
  J Biol Chem, 280, 19393-19400.  
15802643 O.Y.Lubman, R.Kopan, G.Waksman, and S.Korolev (2005).
The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4 through 7 preserve an ankyrin fold.
  Protein Sci, 14, 1274-1281.
PDB code: 1ymp
15677444 R.Fagerlund, L.Kinnunen, M.Köhler, I.Julkunen, and K.Melén (2005).
NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4.
  J Biol Chem, 280, 15942-15951.  
15706086 Y.Kabe, K.Ando, S.Hirao, M.Yoshida, and H.Handa (2005).
Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus.
  Antioxid Redox Signal, 7, 395-403.  
15033982 A.Chantôme, A.Pance, N.Gauthier, D.Vandroux, J.Chenu, E.Solary, J.F.Jeannin, and S.Reveneau (2004).
Casein kinase II-mediated phosphorylation of NF-kappaB p65 subunit enhances inducible nitric-oxide synthase gene transcription in vivo.
  J Biol Chem, 279, 23953-23960.  
15215520 C.H.Croy, S.Bergqvist, T.Huxford, G.Ghosh, and E.A.Komives (2004).
Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution.
  Protein Sci, 13, 1767-1777.  
15140882 G.Xiao, A.Fong, and S.C.Sun (2004).
Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation.
  J Biol Chem, 279, 30099-30105.  
14573596 H.Pang, M.Bartlam, Q.Zeng, H.Miyatake, T.Hisano, K.Miki, L.L.Wong, G.F.Gao, and Z.Rao (2004).
Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.
  J Biol Chem, 279, 1491-1498.
PDB code: 1j1l
15479873 I.M.Verma (2004).
Nuclear factor (NF)-kappaB proteins: therapeutic targets.
  Ann Rheum Dis, 63, ii57-ii61.  
15152081 L.K.Mosavi, T.J.Cammett, D.C.Desrosiers, and Z.Y.Peng (2004).
The ankyrin repeat as molecular architecture for protein recognition.
  Protein Sci, 13, 1435-1448.  
15198984 R.Ran, A.Lu, L.Zhang, Y.Tang, H.Zhu, H.Xu, Y.Feng, C.Han, G.Zhou, A.C.Rigby, and F.R.Sharp (2004).
Hsp70 promotes TNF-mediated apoptosis by binding IKK gamma and impairing NF-kappa B survival signaling.
  Genes Dev, 18, 1466-1481.  
14573599 S.Krzywda, A.M.Brzozowski, H.Higashitsuji, J.Fujita, R.Welchman, S.Dawson, R.J.Mayer, and A.J.Wilkinson (2004).
The crystal structure of gankyrin, an oncoprotein found in complexes with cyclin-dependent kinase 4, a 19 S proteasomal ATPase regulator, and the tumor suppressors Rb and p53.
  J Biol Chem, 279, 1541-1545.
PDB code: 1uoh
15024004 T.Ito, Y.Hozumi, F.Sakane, S.Saino-Saito, H.Kanoh, M.Aoyagi, H.Kondo, and K.Goto (2004).
Cloning and characterization of diacylglycerol kinase iota splice variants in rat brain.
  J Biol Chem, 279, 23317-23326.  
15211579 X.Lu, P.Farmer, J.Rubin, and M.S.Nanes (2004).
Integration of the NfkappaB p65 subunit into the vitamin D receptor transcriptional complex: identification of p65 domains that inhibit 1,25-dihydroxyvitamin D3-stimulated transcription.
  J Cell Biochem, 92, 833-848.  
12566564 A.Kohl, H.K.Binz, P.Forrer, M.T.Stumpp, A.Plückthun, and M.G.Grütter (2003).
Designed to be stable: crystal structure of a consensus ankyrin repeat protein.
  Proc Natl Acad Sci U S A, 100, 1700-1705.
PDB code: 1mj0
14690596 A.Ryo, F.Suizu, Y.Yoshida, K.Perrem, Y.C.Liou, G.Wulf, R.Rottapel, S.Yamaoka, and K.P.Lu (2003).
Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA.
  Mol Cell, 12, 1413-1426.  
12709443 E.Derudder, E.Dejardin, L.L.Pritchard, D.R.Green, M.Korner, and V.Baud (2003).
RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100.
  J Biol Chem, 278, 23278-23284.  
  12683976 H.N.Arst, and M.A.Peñalva (2003).
pH regulation in Aspergillus and parallels with higher eukaryotic regulatory systems.
  Trends Genet, 19, 224-231.  
12624092 H.R.Mott, D.Nietlispach, L.J.Hopkins, G.Mirey, J.H.Camonis, and D.Owen (2003).
Structure of the GTPase-binding domain of Sec5 and elucidation of its Ral binding site.
  J Biol Chem, 278, 17053-17059.
PDB code: 1hk6
14621993 J.Li, S.H.Joo, and M.D.Tsai (2003).
An NF-kappaB-specific inhibitor, IkappaBalpha, binds to and inhibits cyclin-dependent kinase 4.
  Biochemistry, 42, 13476-13483.  
12517341 K.S.Tang, A.R.Fersht, and L.S.Itzhaki (2003).
Sequential unfolding of ankyrin repeats in tumor suppressor p16.
  Structure, 11, 67-73.  
14685242 L.Ganesh, E.Burstein, A.Guha-Niyogi, M.K.Louder, J.R.Mascola, L.W.Klomp, C.Wijmenga, C.S.Duckett, and G.J.Nabel (2003).
The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes.
  Nature, 426, 853-857.  
12972607 M.A.Pratt, T.E.Bishop, D.White, G.Yasvinski, M.Ménard, M.Y.Niu, and R.Clarke (2003).
Estrogen withdrawal-induced NF-kappaB activity and bcl-3 expression in breast cancer cells: roles in growth and hormone independence.
  Mol Cell Biol, 23, 6887-6900.  
14573873 M.E.Zweifel, D.J.Leahy, F.M.Hughson, and D.Barrick (2003).
Structure and stability of the ankyrin domain of the Drosophila Notch receptor.
  Protein Sci, 12, 2622-2632.
PDB code: 1ot8
12949493 M.J.Giffin, J.C.Stroud, D.L.Bates, K.D.von Koenig, J.Hardin, and L.Chen (2003).
Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.
  Nat Struct Biol, 10, 800-806.
PDB code: 1p7h
12832462 S.Beinke, J.Deka, V.Lang, M.P.Belich, P.A.Walker, S.Howell, S.J.Smerdon, S.J.Gamblin, and S.C.Ley (2003).
NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity.
  Mol Cell Biol, 23, 4739-4752.  
12686541 S.Malek, D.B.Huang, T.Huxford, S.Ghosh, and G.Ghosh (2003).
X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex.
  J Biol Chem, 278, 23094-23100.
PDB codes: 1k3z 1oy3
12820969 S.Saccani, S.Pantano, and G.Natoli (2003).
Modulation of NF-kappaB activity by exchange of dimers.
  Mol Cell, 11, 1563-1574.  
12644465 Y.Nam, A.P.Weng, J.C.Aster, and S.C.Blacklow (2003).
Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex.
  J Biol Chem, 278, 21232-21239.  
11801607 A.Birbach, P.Gold, B.R.Binder, E.Hofer, R.de Martin, and J.A.Schmid (2002).
Signaling molecules of the NF-kappa B pathway shuttle constitutively between cytoplasm and nucleus.
  J Biol Chem, 277, 10842-10851.  
11983684 A.Kanayama, J.Inoue, Y.Sugita-Konishi, M.Shimizu, and Y.Miyamoto (2002).
Oxidation of Ikappa Balpha at methionine 45 is one cause of taurine chloramine-induced inhibition of NF-kappa B activation.
  J Biol Chem, 277, 24049-24056.  
11739381 B.Furia, L.Deng, K.Wu, S.Baylor, K.Kehn, H.Li, R.Donnelly, T.Coleman, and F.Kashanchi (2002).
Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins.
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12456660 L.F.Chen, Y.Mu, and W.C.Greene (2002).
Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB.
  EMBO J, 21, 6539-6548.  
12475944 L.M.Budde, C.Wu, C.Tilman, I.Douglas, and S.Ghosh (2002).
Regulation of IkappaBbeta expression in testis.
  Mol Biol Cell, 13, 4179-4194.  
11850407 M.Davis, A.Hatzubai, J.S.Andersen, E.Ben-Shushan, G.Z.Fisher, A.Yaron, A.Bauskin, F.Mercurio, M.Mann, and Y.Ben-Neriah (2002).
Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U.
  Genes Dev, 16, 439-451.  
11971907 P.Knuefermann, P.Chen, A.Misra, S.P.Shi, M.Abdellatif, and N.Sivasubramanian (2002).
Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers.
  J Biol Chem, 277, 23888-23897.  
12456646 P.Michaely, D.R.Tomchick, M.Machius, and R.G.Anderson (2002).
Crystal structure of a 12 ANK repeat stack from human ankyrinR.
  EMBO J, 21, 6387-6396.
PDB code: 1n11
12360211 Q.Li, and I.M.Verma (2002).
NF-kappaB regulation in the immune system.
  Nat Rev Immunol, 2, 725-734.  
11983155 S.Ghosh, and M.Karin (2002).
Missing pieces in the NF-kappaB puzzle.
  Cell, 109, S81-S96.  
  12538160 T.C.Mitchell, B.S.Thompson, J.O.Trent, and C.R.Casella (2002).
A short domain within Bcl-3 is responsible for its lymphocyte survival activity.
  Ann N Y Acad Sci, 975, 132-147.  
12213807 T.Nishi, N.Shimizu, M.Hiramoto, I.Sato, Y.Yamaguchi, M.Hasegawa, S.Aizawa, H.Tanaka, K.Kataoka, H.Watanabe, and H.Handa (2002).
Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo.
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11463387 C.Lee, M.P.Schwartz, S.Prakash, M.Iwakura, and A.Matouschek (2001).
ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal.
  Mol Cell, 7, 627-637.  
11312120 D.Joyce, C.Albanese, J.Steer, M.Fu, B.Bouzahzah, and R.G.Pestell (2001).
NF-kappaB and cell-cycle regulation: the cyclin connection.
  Cytokine Growth Factor Rev, 12, 73-90.  
11707390 F.Michel, M.Soler-Lopez, C.Petosa, P.Cramer, U.Siebenlist, and C.W.Müller (2001).
Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family.
  EMBO J, 20, 6180-6190.
PDB codes: 1k1a 1k1b
11604520 H.Poulsen, J.Nilsson, C.K.Damgaard, J.Egebjerg, and J.Kjems (2001).
CRM1 mediates the export of ADAR1 through a nuclear export signal within the Z-DNA binding domain.
  Mol Cell Biol, 21, 7862-7871.  
11238906 J.M.Mingot, E.A.Espeso, E.Díez, and M.A.Peñalva (2001).
Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans PacC transcription factor.
  Mol Cell Biol, 21, 1688-1699.  
11534762 K.Y.Moon, K.S.Ahn, J.Lee, and Y.S.Kim (2001).
Kojic acid, a potential inhibitor of NF-kappaB activation in transfectant human HaCaT and SCC-13 cells.
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11336677 T.A.Edwards, S.E.Pyle, R.P.Wharton, and A.K.Aggarwal (2001).
Structure of Pumilio reveals similarity between RNA and peptide binding motifs.
  Cell, 105, 281-289.
PDB code: 3h3d
11416149 T.T.Huang, and S.Miyamoto (2001).
Postrepression activation of NF-kappaB requires the amino-terminal nuclear export signal specific to IkappaBalpha.
  Mol Cell Biol, 21, 4737-4747.  
11416157 W.F.Tam, W.Wang, and R.Sen (2001).
Cell-specific association and shuttling of IkappaBalpha provides a mechanism for nuclear NF-kappaB in B lymphocytes.
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10938133 A.M.DeSandro, U.M.Nagarajan, and J.M.Boss (2000).
Associations and interactions between bare lymphocyte syndrome factors.
  Mol Cell Biol, 20, 6587-6599.  
10637284 B.Jungnickel, A.Staratschek-Jox, A.Bräuninger, T.Spieker, J.Wolf, V.Diehl, M.L.Hansmann, K.Rajewsky, and R.Küppers (2000).
Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.
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10842307 D.A.Jans, C.Y.Xiao, and M.H.Lam (2000).
Nuclear targeting signal recognition: a key control point in nuclear transport?
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  11124807 D.H.Lum, P.E.Kuwabara, D.Zarkower, and A.M.Spence (2000).
Direct protein-protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in C. elegans.
  Genes Dev, 14, 3153-3165.  
  10757765 D.J.Begun, and P.Whitley (2000).
Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.
  Genetics, 154, 1231-1238.  
10660298 E.A.Drier, S.Govind, and R.Steward (2000).
Cactus-independent regulation of Dorsal nuclear import by the ventral signal.
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10723801 M.Karin, and M.Delhase (2000).
The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling.
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10837071 M.Karin, and Y.Ben-Neriah (2000).
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
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10713178 S.P.Hehner, T.G.Hofmann, A.Ushmorov, O.Dienz, I.Wing-Lan Leung, N.Lassam, C.Scheidereit, W.Dröge, and M.L.Schmitz (2000).
Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IkappaB kinase complex.
  Mol Cell Biol, 20, 2556-2568.  
10669735 S.Sachdev, S.Bagchi, D.D.Zhang, A.C.Mings, and M.Hannink (2000).
Nuclear import of IkappaBalpha is accomplished by a ran-independent transport pathway.
  Mol Cell Biol, 20, 1571-1582.  
10655476 T.T.Huang, N.Kudo, M.Yoshida, and S.Miyamoto (2000).
A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes.
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11007957 W.Vanden Berghe, L.Vermeulen, G.De Wilde, K.De Bosscher, E.Boone, and G.Haegeman (2000).
Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6.
  Biochem Pharmacol, 60, 1185-1195.  
  10924851 Y.M.Janssen-Heininger, M.E.Poynter, and P.A.Baeuerle (2000).
Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB.
  Free Radic Biol Med, 28, 1317-1327.  
10611964 A.Kaffman, and E.K.O'Shea (1999).
Regulation of nuclear localization: a key to a door.
  Annu Rev Cell Dev Biol, 15, 291-339.  
11228742 B.Kaltschmidt, T.Sparna, and C.Kaltschmidt (1999).
Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.
  Antioxid Redox Signal, 1, 129-144.  
10647779 C.DeLuca, H.Kwon, R.Lin, M.Wainberg, and J.Hiscott (1999).
NF-kappaB activation and HIV-1 induced apoptosis.
  Cytokine Growth Factor Rev, 10, 235-253.  
  10490645 E.W.Harhaj, and S.C.Sun (1999).
Regulation of RelA subcellular localization by a putative nuclear export signal and p50.
  Mol Cell Biol, 19, 7088-7095.  
10488331 K.Rittinger, J.Budman, J.Xu, S.Volinia, L.C.Cantley, S.J.Smerdon, S.J.Gamblin, and M.B.Yaffe (1999).
Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding.
  Mol Cell, 4, 153-166.
PDB codes: 1qja 1qjb
11232326 M.Delhase, and M.Karin (1999).
The I kappa B kinase: a master regulator of NF-kappa B, innate immunity, and epidermal differentiation.
  Cold Spring Harb Symp Quant Biol, 64, 491-503.  
10488062 M.Karin (1999).
The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation.
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10361086 M.R.Groves, and D.Barford (1999).
Topological characteristics of helical repeat proteins.
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  10368277 P.Cramer, and C.W.Müller (1999).
A firm hand on NFkappaB: structures of the IkappaBalpha-NFkappaB complex.
  Structure, 7, R1-R6.  
  10454581 R.Weil, H.Sirma, C.Giannini, D.Kremsdorf, C.Bessia, C.Dargemont, C.Bréchot, and A.Israël (1999).
Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha.
  Mol Cell Biol, 19, 6345-6354.  
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The NF-kappaB/Rel family of transcription factors in oncogenic transformation and apoptosis.
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10521480 S.D.Shumway, M.Maki, and S.Miyamoto (1999).
The PEST domain of IkappaBalpha is necessary and sufficient for in vitro degradation by mu-calpain.
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10431175 S.G.Sedgwick, and S.J.Smerdon (1999).
The ankyrin repeat: a diversity of interactions on a common structural framework.
  Trends Biochem Sci, 24, 311-316.  
11232330 T.Huxford, S.Malek, and G.Ghosh (1999).
Structure and mechanism in NF-kappa B/I kappa B signaling.
  Cold Spring Harb Symp Quant Biol, 64, 533-540.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.