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General Information:

Id:	4,118
Diseases:	Multiple sclerosis - [OMIM]
Organism:	Mammalia
Publication type:	review
Reference:	Arnason BG et al.(2013) Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis Mult. Scler. 19: 130-136 [PMID: 23034287]

Interaction Information:

Comment	ACTH binds to all five melanocortin receptors (MCRs). MC1R is expressed in skin, in melanocytes and monocytes, in neutrophils and lymphocytes, central nervous system (CNS), and in microglia and astrocytes.
Formal Description Interaction-ID: 42428	gene/protein ACTH interacts (colocalizes) with gene/protein MC1R

Comment	ACTH binds to all five melanocortin receptors (MCRs). MC2R, the adrenal receptor underlying the steroidogenic actions of ACTH, is also found in osteoblasts and skin.
Formal Description Interaction-ID: 42492	gene/protein ACTH interacts (colocalizes) with gene/protein MC2R MC2R is implicated in adrenal steroidogenesis.
Drugbank entries	Show/Hide entries for MC2R
Drugbank DB01284	Cosyntropin antagonist MC2R
Drugbank DB01285	Corticotropin agonist MC2R
Drugbank DB01284	Cosyntropin antagonist MC2R
Drugbank DB01285	Corticotropin agonist MC2R

Comment	ACTH binds to all five melanocortin receptors (MCRs). MC3R is found in the hypothalamus and limbic system.
Formal Description Interaction-ID: 42493	gene/protein ACTH interacts (colocalizes) with gene/protein MC3R

Comment	ACTH binds to all five melanocortin receptors (MCRs). MC4R, the dominant CNS receptor, is expressed in the cortex, thalamus, hypothalamus, brain stem and spinal cord.
Formal Description Interaction-ID: 42494	gene/protein ACTH interacts (colocalizes) with gene/protein MC4R

Comment	ACTH binds to all five melanocortin receptors (MCRs). MC5R, widely distributed in exocrine glands, is also found in lymphocytes.
Formal Description Interaction-ID: 42495	gene/protein ACTH interacts (colocalizes) with gene/protein MC5R

Comment	ACTH gel (H.P. Acthar Gel), a slow-release formulation of full-sequence ACTH (1-39), contains additional biologically active POMC peptides and has been used for decades to treat multiple sclerosis (MS) exacerbations.
Formal Description Interaction-ID: 42496	drug/chemical compound Corticotropin decreases_activity of disease Multiple sclerosis
Drugbank entries	Show/Hide entries for Corticotropin
Drugbank DB01285	Corticotropin agonist MC2R
Drugbank DB01285	Corticotropin agonist CRH
Drugbank DB01285	Corticotropin agonist MC2R
Drugbank DB01285	Corticotropin agonist CRH

Comment	ACTH can be cleaved to form alpha-MSH.
Formal Description Interaction-ID: 42497	gene/protein ACTH affects_quantity of gene/protein Alpha-MSH

Comment	ACTH and alpha-, beta- and gamma-MSH comprise the melanocortins.
Formal Description Interaction-ID: 42498	gene/protein ACTH affects_activity of gene/protein Melanocortin

Comment	ACTH and alpha-, beta- and gamma-MSH comprise the melanocortins.
Formal Description Interaction-ID: 42499	gene/protein Alpha-MSH affects_activity of gene/protein Melanocortin

Comment	Melanocortins are anti-inflammatory at cellular (i.e. directly suppressing immunocytes) and system levels (i.e. nervous system and glucocorticoid-mediated immune-system downregulation).
Formal Description Interaction-ID: 42500	gene/protein Melanocortin increases_activity of process negative regulation of inflammatory response at cellular and system levels

Comment	Melanocortins inhibit innate immune system cells widely, including macrophages peripherally and microglia in the CNS.
Formal Description Interaction-ID: 42501	gene/protein Melanocortin decreases_activity of process innate immune response of e.g. macrophages peripherally and microglia in the CNS

Comment	Melanocortins inhibit innate immune system cells widely, including macrophages peripherally and microglia in the CNS.
Formal Description Interaction-ID: 42502	gene/protein Melanocortin decreases_activity of tissue/cell line macrophage (macrophages peripherally)

Comment	Melanocortins inhibit innate immune system cells widely, including macrophages peripherally and microglia in the CNS.
Formal Description Interaction-ID: 42503	gene/protein Melanocortin decreases_activity of tissue/cell line microglia in CNS

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42504	gene/protein MC4R increases_activity of process neurotransmitter secretion

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42505	gene/protein MC4R increases_quantity of drug/chemical compound Noradrenaline

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42506	gene/protein MC4R increases_quantity of drug/chemical compound Acetylcholine
Drugbank entries	Show/Hide entries for
Drugbank DB03128	Acetylcholine not specified ACHE
Drugbank DB03128	Acetylcholine not specified ACHE

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42507	gene/protein MC4R increases_quantity of drug/chemical compound Dopamine
Drugbank entries	Show/Hide entries for
Drugbank DB00988	Dopamine agonist DRD1
Drugbank DB00988	Dopamine ligand DBH
Drugbank DB00988	Dopamine agonist DRD5
Drugbank DB00988	Dopamine agonist DRD2
Drugbank DB00988	Dopamine agonist DRD3
Drugbank DB00988	Dopamine agonist DRD4
Drugbank DB00988	Dopamine inducer SLC6A3

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42508	drug/chemical compound Noradrenaline affects_activity of tissue/cell line microglia

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42509	drug/chemical compound Acetylcholine affects_activity of tissue/cell line microglia
Drugbank entries	Show/Hide entries for Acetylcholine
Drugbank DB03128	Acetylcholine not specified ACHE
Drugbank DB03128	Acetylcholine not specified ACHE

Comment	Stimulation of brain-expressed MC4Rs increases central release of neurotransmitters (e.g. noradrenalin (NA), acetylcholine (ACh), dopamine (DA)) that can quell microglia and, via descending neural pathways, triggers release in the periphery of anti-inflammatory NA and ACh from sympathetic and parasympathetic nerve endings.
Formal Description Interaction-ID: 42510	drug/chemical compound Dopamine affects_activity of tissue/cell line microglia
Drugbank entries	Show/Hide entries for Dopamine
Drugbank DB00988	Dopamine agonist DRD1
Drugbank DB00988	Dopamine ligand DBH
Drugbank DB00988	Dopamine agonist DRD5
Drugbank DB00988	Dopamine agonist DRD2
Drugbank DB00988	Dopamine agonist DRD3
Drugbank DB00988	Dopamine agonist DRD4
Drugbank DB00988	Dopamine inducer SLC6A3

Comment	Alpha-MSH restrains the nuclear factor-kappaB (NF-kappaB) transcription factor.
Formal Description Interaction-ID: 42511	gene/protein Alpha-MSH decreases_activity of complex/PPI NF-kappaB complex

Comment	Phosphorylation of IkappaB by cytokines, bacterial products, or viruses causes IkappaB degradation.
Formal Description Interaction-ID: 42514	gene/protein Cytokine increases_phosphorylation of gene/protein NFKBI and causes IkappaB degradation

Comment	Phosphorylation of IkappaB by cytokines, bacterial products, or viruses causes IkappaB degradation.
Formal Description Interaction-ID: 42515	gene/protein Cytokine decreases_quantity of gene/protein NFKBI by degradation

Comment	Phosphorylation of IkappaB by cytokines, bacterial products, or viruses causes IkappaB degradation.
Formal Description Interaction-ID: 42516	environment bacterial product increases_phosphorylation of gene/protein NFKBI and causes IkappaB degradation

Comment	Phosphorylation of IkappaB by cytokines, bacterial products, or viruses causes IkappaB degradation.
Formal Description Interaction-ID: 42517	process viral process decreases_quantity of gene/protein NFKBI by degradation

Comment	Phosphorylation of IkappaB by cytokines, bacterial products, or viruses causes IkappaB degradation.
Formal Description Interaction-ID: 42518	process viral process increases_phosphorylation of gene/protein NFKBI and causes IkappaB degradation

Comment	Newly freed NF-kappaB translocates to the nucleus and binds to DNA sequences encoding NF-kappaB-responsive elements that then trigger transcription of target genes.
Formal Description Interaction-ID: 42519	complex/PPI NF-kappaB complex is localized in cellular component nucleus after translocation

Comment	Newly freed NF-kappaB translocates to the nucleus and binds to DNA sequences encoding NF-kappaB-responsive elements that then trigger transcription of target genes.
Formal Description Interaction-ID: 42520	complex/PPI NF-kappaB complex interacts (colocalizes) with cellular component DNA after translocation NF-kappaB binds to DNA sequences encoding NF-kappaB-responsive elements

Comment	Newly freed NF-kappaB translocates to the nucleus and binds to DNA sequences encoding NF-kappaB-responsive elements that then trigger transcription of target genes.
Formal Description Interaction-ID: 42521	complex/PPI NF-kappaB complex increases_activity of process mRNA transcription of target genes

Comment	Tissue-destructive nitric oxide and neopterin release from macrophages (which rises during MS flares) is also reduced by melanocortins.
Formal Description Interaction-ID: 42522	gene/protein Melanocortin decreases_quantity of drug/chemical compound NO from macrophages

Comment	alpha-MSH increases production of anti-inflammatory IL-10. This reinforces the immunosuppressive capacity of alpha-MSH.
Formal Description Interaction-ID: 42523	gene/protein Alpha-MSH increases_quantity of gene/protein IL10

Comment	IL-10 levels are subnormal in progressive MS.
Formal Description Interaction-ID: 42524	disease Multiple sclerosis decreases_quantity of gene/protein IL10

Comment	alpha-MSH and ACTH induce regulatory T cells (Tregs) that suppress disease in the experimental autoimmune encephalomyelitis (EAE) model of MS.
Formal Description Interaction-ID: 42525	gene/protein Alpha-MSH increases_activity of process T cell activation

Comment	Tissue-destructive nitric oxide and neopterin release from macrophages (which rises during MS flares) is also reduced by melanocortins.
Formal Description Interaction-ID: 42536	gene/protein Melanocortin decreases_quantity of drug/chemical compound Neopterin from macrophages

Comment	alpha-MSH and ACTH induce regulatory T cells (Tregs) that suppress disease in the experimental autoimmune encephalomyelitis (EAE) model of MS.
Formal Description Interaction-ID: 42537	gene/protein ACTH increases_activity of process T cell activation

Comment	alpha-MSH and ACTH induce regulatory T cells (Tregs) that suppress disease in the experimental autoimmune encephalomyelitis (EAE) model of MS.
Formal Description Interaction-ID: 42538	tissue/cell line regulatory T-lymphocyte decreases_activity of phenotype experimental autoimmune encephalomyelitis

Comment	ACTH increases tyrosine hydroxylase mRNA, and hence NA synthesis, in SNS ganglion neurons.
Formal Description Interaction-ID: 42539	gene/protein ACTH increases_expression of gene/protein TH ACTH increases tyrosine hydroxylase mRNA.
Drugbank entries	Show/Hide entries for TH
Drugbank DB00120	L-Phenylalanine binder TH
Drugbank DB00135	L-Tyrosine binder TH
Drugbank DB00360	Tetrahydrobiopterin cofactor TH
Drugbank DB00765	Metyrosine binder TH
Drugbank DB03552	Meta-Tyrosine not specified TH
Drugbank DB04400	7,8-Dihydrobiopterin not specified TH
Drugbank DB00120	L-Phenylalanine binder TH
Drugbank DB00135	L-Tyrosine binder TH
Drugbank DB00765	Metyrosine binder TH
Drugbank DB03552	Meta-Tyrosine not specified TH
Drugbank DB04400	7,8-Dihydrobiopterin not specified TH

Comment	ACTH increases tyrosine hydroxylase mRNA, and hence NA synthesis, in SNS ganglion neurons.
Formal Description Interaction-ID: 42540	gene/protein ACTH increases_quantity of drug/chemical compound Noradrenaline in SNS ganglion neurons

Comment	NA modulates inflammation and protects against EAE, suggesting that melanocortin-induced NA release may be relevant in MS, a notion reinforced by findings with the beta2-adrenergic agonist albuterol which, as an add-on to glatiramer acetate, strikingly reduces MS relapses.
Formal Description Interaction-ID: 42566	drug/chemical compound Noradrenaline affects_activity of process inflammatory response

Comment	NA modulates inflammation and protects against EAE, suggesting that melanocortin-induced NA release may be relevant in MS, a notion reinforced by findings with the beta2-adrenergic agonist albuterol which, as an add-on to glatiramer acetate, strikingly reduces MS relapses.
Formal Description Interaction-ID: 42567	drug/chemical compound Noradrenaline decreases_activity of phenotype experimental autoimmune encephalomyelitis

Comment	Melanocortins increase immunosuppressive NA outflow via four reinforcing mechanisms.
Formal Description Interaction-ID: 42568	gene/protein Melanocortin increases_quantity of drug/chemical compound Noradrenaline

Comment	Peripheral cholinergic pathways downregulate inflammatory responses via macrophage-expressed alpha7-nicotinic ACh receptors (AChRs).
Formal Description Interaction-ID: 42570	process cholinergic pathway (peripheral) decreases_activity of process inflammatory response via macrophage-expressed alpha7-nicotinic ACh receptors (AChRs)

Comment	DMVN neuron activation by central alpha-MSH/ACTH triggers ACh release from their efferent endings.
Formal Description Interaction-ID: 42571	gene/protein Alpha-MSH increases_activity of tissue/cell line DMVN neuron and triggers ACh release from their efferent endings

Comment	Released ACh engages monocyte/macrophage alpha7-nicotinic AChRs.
Formal Description Interaction-ID: 42572	drug/chemical compound Acetylcholine increases_activity of gene/protein CHRNA7
Drugbank entries	Show/Hide entries for Acetylcholine or CHRNA7
Drugbank DB03128	Acetylcholine not specified ACHE
Drugbank DB03128	Acetylcholine not specified ACHE
Drugbank DB00184	Nicotine agonist CHRNA7
Drugbank DB00237	Butabarbital antagonist CHRNA7
Drugbank DB00241	Butalbital antagonist CHRNA7
Drugbank DB00306	Talbutal antagonist CHRNA7
Drugbank DB00312	Pentobarbital antagonist CHRNA7
Drugbank DB00418	Secobarbital antagonist CHRNA7
Drugbank DB00463	Metharbital antagonist CHRNA7
Drugbank DB00599	Thiopental antagonist CHRNA7
Drugbank DB00674	Galantamine allosteric modulator CHRNA7
Drugbank DB00794	Primidone antagonist CHRNA7
Drugbank DB00849	Methylphenobarbital antagonist CHRNA7
Drugbank DB01174	Phenobarbital antagonist CHRNA7
Drugbank DB01273	Varenicline agonist CHRNA7
Drugbank DB01351	Amobarbital antagonist CHRNA7
Drugbank DB01352	Aprobarbital antagonist CHRNA7
Drugbank DB01353	Butethal antagonist CHRNA7
Drugbank DB01354	Heptabarbital antagonist CHRNA7
Drugbank DB01355	Hexobarbital antagonist CHRNA7
Drugbank DB01483	Barbital antagonist CHRNA7
Drugbank DB01496	Barbituric acid derivative antagonist CHRNA7

Comment	DMVN neuron activation by central alpha-MSH/ACTH triggers ACh release from their efferent endings.
Formal Description Interaction-ID: 42573	gene/protein ACTH increases_activity of tissue/cell line DMVN neuron and triggers ACh release from their efferent endings

Comment	Systemic ACTH or alpha-MSH given peripherally, heighten CNS-restricted actions like motivation, attention, arousal, learning and memory.
Formal Description Interaction-ID: 42574	gene/protein ACTH increases_activity of process motivation

Comment	Systemic ACTH or alpha-MSH given peripherally, heighten CNS-restricted actions like motivation, attention, arousal, learning and memory.
Formal Description Interaction-ID: 42575	gene/protein ACTH increases_activity of process attention

Comment	Systemic ACTH or alpha-MSH given peripherally, heighten CNS-restricted actions like motivation, attention, arousal, learning and memory.
Formal Description Interaction-ID: 42576	gene/protein ACTH increases_activity of process arousal

Comment	Systemic ACTH or alpha-MSH given peripherally, heighten CNS-restricted actions like motivation, attention, arousal, learning and memory.
Formal Description Interaction-ID: 42577	gene/protein ACTH increases_activity of process learning or memory

Comment	LC (locus ceruleus) ablation causes NA depletion throughout the cortex and frees microglia to make proinflammatory cytokines. Thus, decreased LC metabolism in MS links to cognitive impairment.
Formal Description Interaction-ID: 42578	phenotype decreased locus ceruleus metabolism level cooccurs with phenotype cognitive impairment

Comment	Released NA, bound to beta2-adrenegic receptors on microglia, promotes microglial quiescence.
Formal Description Interaction-ID: 42580	drug/chemical compound Noradrenaline decreases_activity of tissue/cell line microglia if bound to beta2-adrenegic receptors on microglia

Comment	LC (locus ceruleus) ablation causes NA depletion throughout the cortex and frees microglia to make proinflammatory cytokines. Thus, decreased LC metabolism in MS links to cognitive impairment.
Formal Description Interaction-ID: 42581	tissue/cell line locus ceruleus affects_quantity of drug/chemical compound Noradrenaline in the cortex

Comment	LC (locus ceruleus) ablation causes NA depletion throughout the cortex and frees microglia to make proinflammatory cytokines. Thus, decreased LC metabolism in MS links to cognitive impairment.
Formal Description Interaction-ID: 42582	tissue/cell line locus ceruleus affects_activity of tissue/cell line microglia in the cortex

Comment	LC (locus ceruleus) ablation causes NA depletion throughout the cortex and frees microglia to make proinflammatory cytokines. Thus, decreased LC metabolism in MS links to cognitive impairment.
Formal Description Interaction-ID: 42583	tissue/cell line locus ceruleus affects_quantity of gene/protein Proinflammatory cytokine in the cortex

Comment	Glutamate activates microglia.
Formal Description Interaction-ID: 42584	drug/chemical compound Glutamate increases_activity of tissue/cell line microglia

Comment	In MS, CNS-restricted proinflammatory cytokines (e.g. TNF-alpha) made by microglia are upregulated, whereas anti-inflammatory cytokines (e.g. IL-10) are suppressed.
Formal Description Interaction-ID: 42585	disease Multiple sclerosis increases_quantity of gene/protein Proinflammatory cytokine (CNS-restricted proinflammatory cytokines made by microglia)

Comment	In MS, CNS-restricted proinflammatory cytokines (e.g. TNF-alpha) made by microglia are upregulated, whereas anti-inflammatory cytokines (e.g. IL-10) are suppressed.
Formal Description Interaction-ID: 42586	disease Multiple sclerosis increases_quantity of gene/protein TNF (CNS-restricted TNF-alpha made by microglia)
Drugbank entries	Show/Hide entries for TNF
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor TNF

Comment	In MS, CNS-restricted proinflammatory cytokines (e.g. TNF-alpha) made by microglia are upregulated, whereas anti-inflammatory cytokines (e.g. IL-10) are suppressed.
Formal Description Interaction-ID: 42587	disease Multiple sclerosis decreases_quantity of gene/protein Antiinflammatory cytokine (CNS-restricted antiinflammatory cytokines made by microglia)

Comment	In MS, CNS-restricted proinflammatory cytokines (e.g. TNF-alpha) made by microglia are upregulated, whereas anti-inflammatory cytokines (e.g. IL-10) are suppressed.
Formal Description Interaction-ID: 42588	disease Multiple sclerosis decreases_quantity of gene/protein IL10 (CNS-restricted antiinflammatory cytokines made by microglia)

Comment	Melanocortins bound to MC1Rs on activated microglia suppress production of the proinflammatory mediators TNF-alpha, IL-6 and nitric oxide.
Formal Description Interaction-ID: 42589	gene/protein Melanocortin decreases_quantity of gene/protein TNF if melanocortins are bound to MC1Rs on activated microglia
Drugbank entries	Show/Hide entries for TNF
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor TNF

Comment	Melanocortins bound to MC1Rs on activated microglia suppress production of the proinflammatory mediators TNF-alpha, IL-6 and nitric oxide (NO).
Formal Description Interaction-ID: 42590	gene/protein Melanocortin decreases_quantity of gene/protein IL6 if melanocortins are bound to MC1Rs on activated microglia
Drugbank entries	Show/Hide entries for IL6
Drugbank DB01404	Ginseng antagonist IL6
Drugbank DB01404	Ginseng antagonist IL6

Comment	Melanocortins bound to MC1Rs on activated microglia suppress production of the proinflammatory mediators TNF-alpha, IL-6 and nitric oxide (NO).
Formal Description Interaction-ID: 42591	gene/protein Melanocortin interacts (colocalizes) with gene/protein MC1R on activated microglia

Comment	ACTH, contrary to steroids, promotes osteoblast differentiation from an immature into a mineralizing phenotype and counteracts dexamethasone-induced osteoblast apoptosis.
Formal Description Interaction-ID: 42592	gene/protein ACTH increases_activity of process osteoblast differentiation

Comment	Alpha-MSH restrains the nuclear factor-kappaB (NF-kappaB) transcription factor.
Formal Description Interaction-ID: 106880	gene/protein Alpha-MSH decreases_activity of complex/PPI NF-kappaB complex via restraining the NF-kappaB transcription factor

Comment	Newly freed NF-kappaB translocates to the nucleus and binds to DNA sequences encoding NF-kappaB-responsive elements that then trigger transcription of target genes.
Formal Description Interaction-ID: 106890	complex/PPI NF-kappaB complex increases_activity of complex/PPI NF-kappaB complex