Page last updated: 2024-10-24

NF-kappaB p50/p65 complex

Definition

Target type: cellularcomponent

A heterodimer of NF-kappa B p50 and p65 subunits. [GO:add, PMID:20393192, PMID:9299584]

The NF-κB p50/p65 complex is a dimeric transcription factor that plays a crucial role in regulating gene expression in response to a wide variety of stimuli, including inflammation, infection, and stress. The complex is composed of two subunits: p50 and p65. p50 is a DNA-binding subunit, while p65 is an activator subunit. Both subunits are members of the Rel family of transcription factors. They share a conserved Rel homology domain (RHD) that is responsible for DNA binding, dimerization, and interaction with other proteins. The RHD is located in the N-terminal region of the protein. The p50 subunit is generated by proteolytic processing of the p105 precursor protein. p65 is encoded by the RELA gene.

The p50/p65 complex resides in the cytoplasm in its inactive form, bound to an inhibitory protein called IκBα. Upon stimulation, IκBα is phosphorylated and degraded, releasing the NF-κB complex. The complex translocates to the nucleus, where it binds to specific DNA sequences called NF-κB binding sites. These sites are located in the promoter regions of target genes, and their binding by NF-κB activates gene transcription.

The cellular component of the NF-κB p50/p65 complex can be described as follows:

* **Cytoplasm:** In its inactive state, the complex is located in the cytoplasm, bound to the inhibitory protein IκBα. This ensures that NF-κB is not constitutively active and can be activated only in response to appropriate stimuli.
* **Nucleus:** Upon stimulation, the complex translocates to the nucleus, where it interacts with DNA and activates gene transcription. This translocation is mediated by the nuclear localization signal (NLS) present in the p65 subunit.
* **DNA:** The p50 subunit of the complex directly binds to DNA at specific NF-κB binding sites. This binding is critical for the activation of target genes.
* **Other proteins:** The NF-κB complex interacts with a variety of other proteins, including coactivators, corepressors, and other transcription factors. These interactions contribute to the regulation of gene expression and the modulation of cellular responses to various stimuli.

The NF-κB p50/p65 complex is a complex and highly regulated system that plays a critical role in many cellular processes. It is a key player in the inflammatory response, immune function, cell survival, and development.'
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Proteins (2)

ProteinDefinitionTaxonomy
Nuclear factor NF-kappa-B p105 subunitA nuclear factor NF-kappa-B p105 subunit that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
Transcription factor p65A transcription factor p65 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (81)

CompoundDefinitionClassesRoles
beta-lapachonebeta-lapachone : A benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities.

beta-lapachone: antineoplastic inhibitor of reverse transcriptase, DNA topoisomerase, and DNA polymerase
benzochromenone;
orthoquinones
anti-inflammatory agent;
antineoplastic agent;
plant metabolite
phloretindihydrochalconesantineoplastic agent;
plant metabolite
aurinaurin: structurediarylmethane
sanguinarinebenzophenanthridine alkaloid : A specific group of isoquinoline alkaloids that occur only in higher plants and are constituents mainly of the Papaveraceae family.alkaloid antibiotic;
benzophenanthridine alkaloid;
botanical anti-fungal agent
ficusinFicusin: A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.

psoralen : The simplest member of the class of psoralens that is 7H-furo[3,2-g]chromene having a keto group at position 7. It has been found in plants like Psoralea corylifolia and Ficus salicifolia.
psoralensplant metabolite
gibberellic acidgibberellic acid: RN given refers to (1alpha,2beta,4aalpha,4bbeta,10beta)-isomer; structure

gibberellin A3 : A C19-gibberellin that is a pentacyclic diterpenoid responsible for promoting growth and elongation of cells in plants. Initially identified in Gibberella fujikuroi,it differs from gibberellin A1 in the presence of a double bond between C-3 and C-4.
C19-gibberellin;
gibberellin monocarboxylic acid;
lactone;
organic heteropentacyclic compound
mouse metabolite;
plant metabolite
evans blueEvans blue : An organic sodium salt that is the tetrasodium salt of 6,6'-{(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis[diazene-2,1-diyl]}bis(4-amino-5-hydroxynaphthalene-1,3-disulfonate). It is sometimes used as a counterstain, especially in fluorescent methods to suppress background autofluorescence.

Evans Blue: An azo dye used in blood volume and cardiac output measurement by the dye dilution method. It is very soluble, strongly bound to plasma albumin, and disappears very slowly.
organic sodium saltfluorochrome;
histological dye;
sodium channel blocker;
teratogenic agent
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
angelicinangelicin: used as tranquillizer; sedative; or anticonvulsant; structurefuranocoumarin
helenalinhelenalin : A sesquiterpene lactone that is 3,3a,4,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione substituted by a hydroxy group at position 4, methyl groups at positions 4a and 8 and a methylidene group at position 3 (the 3aS,4S,4aR,7aR,8R,9aR stereoisomer).

helenalin: toxic principle of Helenium microcephalum (smallhead sneezeweed); structure

NF-kappaB inhibitor : An inhibitor of NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), a protein complex involved in the transcription of DNA.
cyclic ketone;
gamma-lactone;
organic heterotricyclic compound;
secondary alcohol;
sesquiterpene lactone
anti-inflammatory agent;
antineoplastic agent;
metabolite;
plant metabolite
ursolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
geroprotector;
plant metabolite
betulinic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
anti-HIV agent;
anti-inflammatory agent;
antimalarial;
antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
plant metabolite
pyrrolidine dithiocarbamatepyrrolidine dithiocarbamate : A member of the class of dithiocarbamic acids that is the N-dithiocarboxy derivative of pyrrolidine.

pyrrolidine dithiocarbamic acid: spelled pyrolidine in J Nutr 1979 reference; RN given refers to parent cpd
dithiocarbamic acids;
pyrrolidines
anticonvulsant;
antineoplastic agent;
geroprotector;
neuroprotective agent;
NF-kappaB inhibitor;
radical scavenger
betulinbetulin : A pentacyclic triterpenoid that is lupane having a double bond at position 20(29) as well as 3beta-hydroxy and 28-hydroxymethyl substituents.

betulin: isolated from various white birch bark (BETULA)
diol;
pentacyclic triterpenoid
analgesic;
anti-inflammatory agent;
antineoplastic agent;
antiviral agent;
metabolite
dehydroleucodinedehydroleucodine: has antimicrobial activity; RN given refers to (3aS-(3aalpha,9aalpha,9bbeta))-isomer
altersolanol aaltersolanol A: isolated from fermentation product of fungus Alternaria porri(Ellis) Ciferri;RN given refers to (1R-(1alpha,2beta,3beta,4alpha))-isomer; structure given in first sourcepentahydroxyanthraquinone
uvaoluvaol: from Vauquelinia corymbosa (Rosaceae)triterpenoidmetabolite
Mexicanin Isesquiterpene lactone
loliolideloliolide: RN given refers to (6S-cis)-isomerbenzofuransmetabolite
erythrodioldiol;
pentacyclic triterpenoid;
primary alcohol;
secondary alcohol
plant metabolite
parthenolidegermacranolide
gefitinibaromatic ether;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
quinazolines;
secondary amino compound;
tertiary amino compound
antineoplastic agent;
epidermal growth factor receptor antagonist
tetrahydrocurcumintetrahydrocurcumin : A beta-diketone that is curcumin in which both of the double bonds have been reduced to single bonds.beta-diketone;
diarylheptanoid;
polyphenol
metabolite
8-(4-benzenesulfonylamino)quinoline8-(4-benzenesulfonylamino)quinoline: has diabetogenic properties; structure given in first source
withanolide dwithanolide D : A withanolide that is 5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione substituted by hydroxy groups at positions 4 and 22 (the 4beta,5beta,6beta,22R stereoisomer). Isolated from Tubocapsicum anomalum and Withania somnifera, it exhibits cytotoxic activity.

withanolide D: structure
20-hydroxy steroid;
4-hydroxy steroid;
delta-lactone;
enone;
epoxy steroid;
ergostanoid;
secondary alcohol;
tertiary alcohol;
withanolide
antineoplastic agent
arnicolide darnicolide D: cytotoxic; from Centipeda minima L.; structure in first sourcesesquiterpene lactone
santamarinesantamarin : A sesquiterpene lactone of the eudesmanolide group.

santamarine: sesquiterpene derivative of costunolide
sesquiterpene lactone
withaferin awithaferin A : A withanolide that is 5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione substituted by hydroxy groups at positions 4 and 27 (the 4beta,5beta,6beta,22R stereoisomer). Isolated from Physalis longifolia, it exhibits cytotoxic activity.

withaferin A: an antiestrogen and phytogenic antineoplastic agent isolated from leaves of Withania somnifera Dun.; structure
27-hydroxy steroid;
4-hydroxy steroid;
delta-lactone;
enone;
epoxy steroid;
ergostanoid;
primary alcohol;
secondary alcohol;
withanolide
antineoplastic agent;
apoptosis inducer
rocaglamiderocaglamide : An organic heterotricyclic compound that is 2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan substituted by hydroxy groups at positions 1 and 8b, methoxy groups at positions 6 and 8, a 4-methoxyphenyl group at position 3a, a phenyl group at position 3 and a N,N-dimethylcarbamoyl group at position 1. Isolated from Aglaia odorata and Aglaia duperreana, it exhibits antineoplastic activity.

rocaglamide: RN refers to (1alpha,2alpha,3beta,3abeta,8bbeta)-isomer; isolated from stems of Aglaia elliptifolia; structure given in first source
monocarboxylic acid amide;
monomethoxybenzene;
organic heterotricyclic compound
antileishmanial agent;
antineoplastic agent;
metabolite
bortezomibamino acid amide;
L-phenylalanine derivative;
pyrazines
antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
8-deoxygartanin8-deoxygartanin: a butyrylcholinesterase inhibitor; isolated from Garcinia mangostana; structure in first sourcexanthones
aglafolineaglafolin : A heterotricyclic compound based on a 2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a and methoxy groups at C-6 and C-8. A platelet aggregation inhibitor found in Aglaia elliptifolia and Aglaia odorata.

aglafoline: a platelet activating factor antagonist; structure given in first source; isolated from Aglaia elliptifolia
methyl ester;
organic heterotricyclic compound
metabolite;
platelet aggregation inhibitor
rocaglaolrocaglaol: a cytotoxic cyclopenta(b)benzofuran from the bark of Aglaia crassinervia; structure in first source
tosylphenylalanyl chloromethyl ketoneN-tosyl-L-phenylalanyl chloromethyl ketone : The N-tosyl derivative of L-phenylalanyl chloromethyl ketone.

Tosylphenylalanyl Chloromethyl Ketone: An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.
alpha-chloroketone;
sulfonamide
alkylating agent;
serine proteinase inhibitor
11alpha,13-dihydrohelenalinsesquiterpene lactone
resveratroltrans-resveratrol : A resveratrol in which the double bond has E configuration.resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
2-hydroxycinnamic acid2-coumaric acid : A monohydroxycinnamic acid in which the hydroxy substituent is located at C-2 of the phenyl ring.

trans-2-coumaric acid : The trans-isomer of 2-coumaric acid.
2-coumaric acid;
phenols
antioxidant;
metabolite
isoliquiritigeninchalconesantineoplastic agent;
biological pigment;
EC 1.14.18.1 (tyrosinase) inhibitor;
GABA modulator;
geroprotector;
metabolite;
NMDA receptor antagonist
xanthohumolxanthohumol : A member of the class of chalcones that is trans-chalcone substituted by hydroxy groups at positions 4, 2' and 4', a methoxy group at position 6' and a prenyl group at position 3'. Isolated from Humulus lupulus, it induces apoptosis in human malignant glioblastoma cells.

xanthohumol: from hop plant, Humulus lupulus
aromatic ether;
chalcones;
polyphenol
anti-HIV-1 agent;
antineoplastic agent;
antiviral agent;
apoptosis inducer;
EC 2.3.1.20 (diacylglycerol O-acyltransferase) inhibitor;
metabolite
5H-quinolino[8,7-c][1,2]benzothiazine 6,6-dioxidebenzothiazine
parthenolide, (1ar-(1ar*,4e,7as*,10as*,10br*))-isomergermacranolide
3-(3-fluoro-4-methoxyphenyl)-5-phenyl-7-furo[3,2-g][1]benzopyranonediarylheptanoid
sideroxylinsideroxylin : A monomethoxyflavone that is flavone substituted by a methoxy group at position 7, hydroxy groups at positions 5 and 4' and methyl groups at positions 6 and 8. It has been isolated from Hydrastis canadensis and Eucalyptus species.

sideroxylin: from Hydrastis canadensis; structure in first source
dihydroxyflavone;
monomethoxyflavone
plant metabolite
scopoletinhydroxycoumarinplant growth regulator;
plant metabolite
vomifoliol(6S,9R)-vomifoliol : A (6S)-vomifoliol with a R configuration for the hydroxy group at position 9.

blumenol A: a phytotoxin isolated from Oryza sativa Awaakamai; structure in first source

vomifoliol : A fenchane monoterpenoid that is 3,5,5-trimethylcyclohex-2-en-1-one substituted by a hydroxy and a (1E)-3-hydroxybut-1-en-1-yl group at position 4.
(6S)-vomifoliolmetabolite;
phytotoxin
hymecromoneHymecromone: A coumarin derivative possessing properties as a spasmolytic, choleretic and light-protective agent. It is also used in ANALYTICAL CHEMISTRY TECHNIQUES for the determination of NITRIC ACID.hydroxycoumarinantineoplastic agent;
hyaluronic acid synthesis inhibitor
lipoxin a4lipoxin A4 : A C20 hydroxy fatty acid having (5S)-, (6R)- and (15S)-hydroxy groups as well as (7E)- (9E)-, (11Z)- and (13E)-double bonds.

lipoxin A4: an antifibrolytic agent; structure given in first source; a role in ASPIRIN antiinflammatory activity
hydroxy polyunsaturated fatty acid;
lipoxin;
long-chain fatty acid
human metabolite;
metabolite
buteinchalcones;
polyphenol
antineoplastic agent;
antioxidant;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
geroprotector;
hypoglycemic agent;
plant metabolite;
radiosensitizing agent;
tyrosine kinase inhibitor
costunolidegermacranolide;
heterobicyclic compound
anthelminthic drug;
antiinfective agent;
antineoplastic agent;
antiparasitic agent;
antiviral drug;
metabolite
molephantininmolephantinin: germacranolide from Elephantopus mollis; RN given refers to (3aR-(3aR*,4S*(E),6E,9Z,11S*,11aS*))-isomer; structure in first sourcegermacranolide
gartaningartanin : A member of the class of xanthones that is 9H-xanthen-9-one substituted by hydroxy groups at positions 1, 3, 5 and 8 and prenyl groups at positions 2 and 4.polyphenol;
xanthones
antineoplastic agent;
plant metabolite
mangostinalpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities.

mangostin: xanthone from rind of Garcinia mangostana Linn. fruit
aromatic ether;
phenols;
xanthones
antimicrobial agent;
antineoplastic agent;
antioxidant;
plant metabolite
3,3',4-o-trimethylellagic acid3,7,8-tri-O-methylellagic acid: structure given in first sourcetannin
4-hydroxychalcone4-hydroxychalcone : A member of the class of chalcones that is trans-chalcone substituted by a hydroxy group at position 4.

4-hydroxychalcone: structure in first source
chalcones;
phenols
antihypertensive agent;
plant metabolite
andrographolidecarbobicyclic compound;
gamma-lactone;
labdane diterpenoid;
primary alcohol;
secondary alcohol
anti-HIV agent;
anti-inflammatory drug;
antineoplastic agent;
metabolite
bay 11-7082(E)-3-tosylacrylonitrile : A nitrile that is acrylonitrile in which the hydrogen located beta,trans to the cyano group is replaced by a tosyl group. It is an inhibitor of cytokine-induced IkappaB-alpha phosphorylation in cells.nitrile;
sulfone
apoptosis inducer;
EC 2.7.11.10 (IkappaB kinase) inhibitor;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor;
non-steroidal anti-inflammatory drug;
platelet aggregation inhibitor
furanoheliangolidefuranoheliangolide: structure in first source
beta-Mangostinxanthones
9-Hydroxycalabaxanthonexanthones
flavokawain Cflavokawain C: antineoplastic from roots of Kava (Piper methysticum Forst); structure in first sourcechalcones
rehmannic acidrehmannic acid: toxic principle, triterpene acid from Lantana camara; RN given refers to (22beta-(Z))-isomer; structure
3-o-methylbutein3-O-methylbutein: RN given refers to (E)-isomer; structure given in first sourcechalcones
goniothalamingoniothalamin: has antineoplastic activity; structure given in first source
hylin
spc-839SPC-839: an inhibitor of activator protein 1; structure in first source
fr 1480835Z-7-oxozeaenol : A macrolide that is the 7-oxo derivative of zeaenol (the 5Z stereoisomer). Isolated from Fungi, it exhibits cytotoxic, antibacterial and inhibitory activity against NF-kappaB.aromatic ether;
macrolide;
phenols;
secondary alcohol;
secondary alpha-hydroxy ketone
antibacterial agent;
antineoplastic agent;
metabolite;
NF-kappaB inhibitor
LL-Z1640-1macrolide;
resorcinols
metabolite
sp 100030N-(3,5-bis(trifluoromethyl)phenyl)-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide: transcription factor inhibitor specific to T-cells
tirotundintirotundin: structure in first source
cumambrin bcumambrin B: RN given for (3aR-(3aalpha,4alpha,6alpha,6aalpha,9aalpha,9bbeta))-isomer; isolated from Chrysanthemum boreale; structure in first source
chamissonolidechamissonolide: structure given in first source
Cycloartobiloxanthonecycloartobiloxanthone: a flavonoid isolated from stem bark of Artocarpus gomezianus; has antineoplastic propertiespyranoxanthones
6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide: structure in first souce
silvestrolsilvestrol : An organic heterotricyclic compound that consists of a 2,3,3a,8b-tetrahydro-H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a, a methoxy group at C-8 and a 1,4-dioxan-2-yloxy group at position C-6 which in turn is substituted by a methoxy group at position 3 and a 1,2-dihydroxyethyl group at position 6. Isolated from Aglaia silvestris, it exhibits antineoplastic activity.

silvestrol: isolated from the fruit and twig of Aglaia silvestris
dioxanes;
ether;
methyl ester;
organic heterotricyclic compound
antineoplastic agent;
metabolite
2alpha,3beta-dihydroxy-20(29)-lupen-28-oic acid2alpha,3beta-dihydroxy-20(29)-lupen-28-oic acid : A pentacyclic triterpenoid that is betulinic acid carrying an additional alpha-hydroxy group at position 2. It has been isolated from Breynia fruticosa.

alphitolic acid: from the aerial parts of Gouania longipetala; structure in first source
dihydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
lantadene blantadene B: RN given refers to the (22beta)-isomer; from Lantana camara
achalensolideachalensolide: structure in first source
centratherincentratherin: from Eremanthus eriopus (Asteraceae); structure in first source
2,3-dihydro-3beta-O-sulfate withaferin A2,3-dihydro-3beta-O-sulfate withaferin A : A withanolide that is 2,3-dihydrowithaferin A substituted by a sulfoxy group at position 3. Isolated from Physalis longifolia, it exhibits antineoplastic activity.27-hydroxy steroid;
4-hydroxy steroid;
delta-lactone;
epoxy steroid;
ergostanoid;
primary alcohol;
steroid sulfate;
withanolide
antineoplastic agent;
metabolite;
plant metabolite
chrome azurol schrome azurol S: reagent for beryllium determination spectrophotometrically
hydrazinocurcuminhydrazinocurcumin : A pyrazole obtained by cyclocodensation of the two carbonyl groups of curcumin with hydrazine.

hydrazinocurcumin: structure in first source
aromatic ether;
olefinic compound;
polyphenol;
pyrazoles
angiogenesis modulating agent;
antineoplastic agent;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor