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08-SEPTEMBER-2008 09:13:22 - NF-κB Redirected from NFkB Mechanism of NF-κB action. In this figure, the NF-κB heterodimer between Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase IKK. IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements RE. The DNA/NF-κB complex then recruits other proteins such a coactivators and RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function. Mechanism of NF-κB action. In this figure, the NF-κB heterodimer between Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase IKK. IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements RE. The DNA/NF-κB complex then recruits other proteins such a coactivators and RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function.123 Schematic diagram of NF-κB protein structure. There are two structural classes of NF-κB proteins: class I top and class II bottom. Both classes of proteins contain a N-terminal DNA-binding domain DBD, which also servers as a dimerization interface to other NF-κB transcription factors and in addition binds to the inhibitory IκBα protein. The C-terminus of class I proteins contains a number of ankyrin repeats and has transrepression activity. In contrast, the C-terminus of class II proteins has a transactivation function. Schematic diagram of NF-κB protein structure. There are two structural classes of NF-κB proteins: class I top and class II bottom. Both classes of proteins contain a N-terminal DNA-binding domain DBD, which also servers as a dimerization interface to other NF-κB transcription factors and in addition binds to the inhibitory IκBα protein. The C-terminus of class I proteins contains a number of ankyrin repeats and has transrepression activity. In contrast, the C-terminus of class II proteins has a transactivation function.123 Top view of the crystallographic structure PDB 1SVC of a homodimer of the NFKB1 protein green and magenta bound to DNA brown. NFKB1 Identifiers Symbol NFKB1 Entrez 4790 HUGO 7794 OMIM 164011 RefSeq NM_003998 UniProt P19838 Other data Locus Chr. 4 q24 NFKB2 Identifiers Symbol NFKB2 Entrez 4791 HUGO 7795 OMIM 164012 RefSeq NM_002502 UniProt Q00653 Other data Locus Chr. 10 q24 Side view of the crystallographic structure PDB 2RAM of a homodimer of the RELA protein green and magenta bound to DNA brown. RELA Identifiers Symbol RELA Alt. Symbols NFKB3 Entrez 5970 HUGO 9955 OMIM 164014 RefSeq NM_021975 UniProt Q04206 Other data Locus Chr. 11 q13 RELB Identifiers Symbol RELB Entrez 5971 HUGO 9956 OMIM 604758 RefSeq NM_006509 UniProt Q01201 Other data Locus Chr. 19 q13.2-19q13 REL Identifiers Symbol REL Entrez 5966 HUGO 9954 OMIM 164910 RefSeq NM_002908 UniProt Q04864 Other data Locus Chr. 2 p13-p12 NF-κB nuclear factor-kappa B is a protein complex that is a transcription factor. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.12345 NF-κB plays a key role in regulating the immune response to infection. Consistent with this role, incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.6 Contents 1 Discovery 2 Members 3 Structure 4 Activation of NF-κB 5 Inhibitors of NF-κB 6 NF-κB's role in cancer and other diseases 7 NF-κB as a drug target 8 Signaling in immunity 9 Conserved in evolution 10 See also 11 References 12 External links Discovery NF-κB was first discovered in the lab of Nobel Prize laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain enhancer in B cells.7 Members NF-κB family members share structural homology with the retroviral oncoprotein v-Rel, resulting in their classification as NF-κB/Rel proteins.1 There are five proteins in the mammalian NF-κB family:8 NF-κB1 also called p105→p50 - NFKB1 NF-κB2 also called p100→p52 - NFKB2 RelA also named p65 - RELA RelB - RELB c-Rel REL In addition, there are NF-κB proteins in invertebrates, such as the fruit fly Drosophila, sea urchins, sea anemones, and sponges.9 Structure All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA, RelB, and c-Rel, have a transactivation domain in their C-termini. In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, p105, and p100, which undergo processing to generate the mature NF-κB subunits, p50 and p52, respectively. The processing of p105 and p100 is mediated by the ubiquitin/proteasome pathway and involves selective degradation of their C-terminal region containing ankyrin repeats. Whereas the generation of p52 from p100 is a tightly-regulated process, p50 is produced from constitutive processing of p105.1011 Activation of NF-κB Part of NF-κB's importance in regulating cellular responses is that it belongs to the category of rapid-acting primary transcription factors, i.e., transcription factors that are present in cells in an inactive state and do not require new protein synthesis to be activated other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors. This allows NF-κB to act as a first responder to harmful cellular stimuli. Stimulation of a wide variety of cell-surface receptors, such as RANK, TNFR, leads directly to NF-κB activation and fairly rapid changes in gene expression.1 Many bacterial products can activate NF-κB. The identification of Toll-like receptors TLRs as specific pattern recognition molecules and the finding that stimulation of TLRs leads to activation of NF-κB improved our understanding of how different pathogens activate NF-κB. For example, studies have identified TLR4 as the receptor for the LPS component of Gram-Negative bacteria.12 TLRs are key regulators of both innate and adaptive immune responses.13 Unlike RelA, RelB, and c-Rel, the p50 and p52 NF-κB subunits do not contain transactivation domains in their C terminal halves. Nevertheless, the p50 and p52 NF-κB members play critical roles in modulating the specificity of NF-κB function. Although homodimers of p50 and p52 are, in general, repressors of κB site transcription, both p50 and p52 participate in target gene transactivation by forming heterodimers with RelA, RelB, or c-Rel.14 In addition, p50 and p52 homodimers also bind to the nuclear protein Bcl-3, and such complexes can function as transcriptional activators.151617 Inhibitors of NF-κB In unstimulated cells, the NF-κB dimers are sequestered in the cytoplasm by a family of inhibitors, called IκBs Inhibitor of κB, which are proteins that contain multiple copies of a sequence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the nuclear localization signals NLS of NF-κB proteins and keep them sequestered in an inactive state in the cytoplasm.18 IκBs are a family of related proteins that have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. Although the IκB family consists of IκBα, IκBβ, IκBγ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the presence of ankyrin repeats in their C-terminal halves, p105 and p100 also function as IκB proteins. Of all the IκB members, IκBγ is unique in that it is synthesized from the nf-kb1 gene using an internal promoter, thereby resulting in a protein that is identical to the C-terminal half of p105.19 The c-terminal half of p100, that is often referred to as IκBδ, also functions as an inhibitor.2021 IκBδ degradation in response to developmental stimuli, such as those transduced through LTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway.2022 Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. This occurs primarily via activation of a kinase called the IκB kinase IKK. IKK is composed of a heterodimer of the catalytic IKK alpha and IKK beta subunits and a master regulatory protein termed NEMO NF-κB essential modulator or IKK gamma. When activated by signals, usually coming from the outside of the cell, the IκB kinase phosphorylates two serine residues located in an IκB regulatory domain. When phosphorylated on these serines e.g., serines 32 and 36 in human IκBα, the IκB inhibitor molecules are modified by a process called ubiquitination, which then leads them to be degraded by a cell structure called the proteasome. With the degradation of the IκB inhibitor, the NF-κB complex is then freed to enter the nucleus where it can 'turn on' the expression of specific genes that have DNA-binding sites for NF-κB nearby. The activation of these genes by NF-κB then leads to the given physiological response, for example, an inflammatory or immune response, a cell survival response, or cellular proliferation. NF-κB turns on expression of its own repressor, IκBα. The newly synthesized IκBα then re-inhibits NF-κB and, thus, forms an auto feedback loop, which results in oscillating levels of NF-κB activity.23 In addition, several viruses, including the AIDS virus HIV, have binding sites for NF-κB that controls the expression of viral genes, which in turn contribute to viral replication or viral pathogenicity. In the case of HIV-1, activation of NF-κB may, at least in part, be involved in activation of the virus from a latent, inactive state.24 YopJ is a factor secreted by Yersinia pestis, the causative agent of plague, that prevents the ubiquitination of IκB. This causes this pathogen to effectively inhibit the NF-κB pathway and thus block the immune response of a human infected with Yersinia.25 NF-κB's role in cancer and other diseases NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die. This is called apoptosis. Defects in NF-κB results in increased susceptibility to apoptosis leading to increased cell death. This is because NF-κB regulates anti-apoptotic genes especially the TRAF1 and TRAF2 and thereby checks the activities of the caspase family of enzymes which are central to most apoptotic processes.26 In tumor cells, NF-κB is active either due to mutations in genes encoding the NF-κB transcription factors themselves or in genes that control NF-κB activity such as IκB genes; in addition, some tumor cells secrete factors that cause NF-κB to become active. Blocking NF-κB can cause tumor cells to stop proliferating, to die, or to become more sensitive to the action of anti-tumor agents. Thus, NF-κB is the subject of much active research among pharmaceutical companies as a target for anti-cancer therapy.27 Because NF-κB controls many genes involved in inflammation, it is not surprising that NF-κB is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, asthma, among others. Many natural products including anti-oxidants that have been promoted to have anti-cancer and anti-inflammatory activity have also been shown to inhibit NF-κB. There is a controversial US patent US patent 6,410,51628 that applies to the discovery and use of agents that can block NF-κB for therapeutic purposes. This patent is involved in several lawsuits, including Ariad v. Lilly. Recent work by Karin,29 Ben-Neriah30 and others has highlighted the importance of the connection between NF-κB, inflammation, and cancer, and underscored the value of therapies that regulate the activity of NF-κB.31 NF-κB as a drug target The discovery that activation of NF-κB nuclear translocation can be separated from the elevation of oxidant stress32 gives an important hint to the development of strategies for NF-κB inhibition. Disulfiram and dithiocarbamates can inhibit the nuclear factor-κB NF-κB signaling cascade.33 Signaling in immunity NF-kB is a major transcription factor that regulates genes responsible for both the innate and adaptive immune response. Upon activation of either the T- or B-cell receptor, NF-kB becomes activated through distinct signaling components. Upon ligation of the T-cell receptor, an adaptor molecule, ZAP70 is recruited via its SH2 domain to the cytoplasmic side of the receptor. ZAP70 helps recruit both LCK and PLC-γ, which causes activation of PKC. Through a cascade of phosphorylation events, the kinase complex is activated and NF-kB is able to enter the nucleus to upregulate genes involved in T-cell development, maturation, and proliferation.34 Conserved in evolution NF-kB is found in a number of simple animals as well. These include cnidarians such as sea anemones and coral, porifera sponges, and insects such as moths, mosquitoes, and fruitflies. The sequencing of the genomes of A. aegypti, A. gambiae, and the fruitfly D. melanogaster has allowed comparative genetic and evolutionary studies on NF-kB. In those insect species, activation of NF-kB is triggered by the Toll pathway which evolved independently in insects and mammals and by the Imd pathway.35 See also IKK2 References ^ a b c d e Gilmore TD 2006. Introduction to NF-κB: players, pathways, perspectives. Oncogene 25 51: 6680-4. doi:10.1038/sj.onc.1209954. PMID 17072321. ^ a b c Brasier AR 2006. The NF-κB regulatory network. Cardiovasc. Toxicol. 6 2: 111-30. doi:10.1385/CT:6:2:111. PMID 17303919. ^ a b c Perkins ND January 2007. Integrating cell-signalling pathways with NF-κB and IKK function. Nat. Rev. Mol. Cell Biol. 8 1: 49-62. doi:10.1038/nrm2083. PMID 17183360. ^ Gilmore TD 1999. The Rel/NF-κB signal transduction pathway: introduction. Oncogene 18 49: 6842-4. doi:10.1038/sj.onc.1203237. PMID 10602459. ^ Tian B, Brasier AR 2003. Identification of a nuclear factor κ B-dependent gene network. Recent Prog. Horm. Res. 58: 95-130. doi:10.1210/rp.58.1.95. PMID 12795416. ^ Albensi BC, Mattson MP 2000. Evidence for the involvement of TNF and NF-κB in hippocampal synaptic plasticity. Synapse 35 2: 151-9. doi:10.1002/SICI1098-239620000235:2151::AID-SYN83.0.CO;2-P. PMID 10611641. ^ Sen R, Baltimore D 1986. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46 5: 705-16. doi:10.1016/0092-86748690346-6. PMID 3091258. ^ Nabel GJ, Verma IM November 1993. Proposed NF-κB/IκB family nomenclature. Genes Dev. 7 11: 2063. PMID 8224837. ^ Ghosh S, May MJ, Kopp EB 1998. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16: 225-60. doi:10.1146/annurev.immunol.16.1.225. PMID 9597130. ^ Karin M, Ben-Neriah Y 2000. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18: 621-63. doi:10.1146/annurev.immunol.18.1.621. PMID 10837071. ^ Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M 2001. Activation by IKKalpha of a second, evolutionary conserved, NF-κB signaling pathway. Science 293 5534: 1495-9. doi:10.1126/science.1062677. PMID 11520989. ^ Doyle SL, O'Neill LA October 2006. Toll-like receptors: from the discovery of NFκB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72 9: 1102-13. doi:10.1016/j.bcp.2006.07.010. PMID 16930560. ^ Hayden MS, West AP, Ghosh S October 2006. NF-κB and the immune response. Oncogene 25 51: 6758-80. doi:10.1038/sj.onc.1209943. PMID 17072327. ^ Li Q, Verma IM 2002. NF-κB regulation in the immune system. Nat. Rev. Immunol. 2 10: 725-34. doi:10.1038/nri910. PMID 12360211. ^ Fujita T, Nolan GP, Liou HC, Scott ML, Baltimore D 1993. The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-κB p50 homodimers. Genes Dev. 7 7B: 1354-63. doi:10.1101/gad.7.7b.1354. PMID 8330739. ^ Franzoso G, Bours V, Park S, Tomita-Yamaguchi M, Kelly K, Siebenlist U 1992. The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-κB-mediated inhibition. Nature 359 6393: 339-42. doi:10.1038/359339a0. PMID 1406939. ^ Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U 1993. The oncoprotein Bcl-3 directly transactivates through κ B motifs via association with DNA-binding p50B homodimers. Cell 72 5: 729-39. doi:10.1016/0092-86749390401-B. PMID 8453667. ^ Jacobs MD, Harrison SC 1998. Structure of an IκBalpha/NF-κB complex. Cell 95 6: 749-58. doi:10.1016/S0092-86740081698-0. PMID 9865693. ^ Inoue J, Kerr LD, Kakizuka A, Verma IM 1992. IκB gamma, a 70 kd protein identical to the C-terminal half of p110 NF-κB: a new member of the IκB family. Cell 68 6: 1109-20. doi:10.1016/0092-86749290082-N. PMID 1339305. ^ a b Basak S, Kim H, Kearns JD, Tergaonkar V, O'dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A 2007. A fourth IκB protein within the NF-κB signaling module. Cell 128 2: 369-81. doi:10.1016/j.cell.2006.12.033. PMID 17254973. . ^ Dobrzanski P, Ryseck RP, Bravo R 1995. Specific inhibition of RelB/p52 transcriptional activity by the C-terminal domain of p100. Oncogene 10 5: 1003-7. PMID 7898917. ^ Lo JC, Basak S, James ES, Quiambo RS, Kinsella MC, Alegre ML, Weih F, Franzoso G, Hoffmann A, Fu YX 2006. Coordination between NF-κB family members p50 and p52 is essential for mediating LTbetaR signals in the development and organization of secondary lymphoid tissues. Blood 107 3: 1048-55. doi:10.1182/blood-2005-06-2452. PMID 16195333. ^ Nelson DE, Ihekwaba AE, Elliott M, Johnson JR, Gibney CA, Foreman BE, Nelson G, See V, Horton CA, Spiller DG, Edwards SW, McDowell HP, Unitt JF, Sullivan E, Grimley R, Benson N, Broomhead D, Kell DB, White MR 2004. Oscillations in NF-κB signaling control the dynamics of gene expression. Science 306 5696: 704-8. doi:10.1126/science.1099962. PMID 15499023. ^ Hiscott J, Kwon H, Génin P January 2001. Hostile takeovers: viral appropriation of the NF-κB pathway. J. Clin. Invest. 107 2: 143-51. doi:10.1172/JCI11918. PMID 11160127. ^ Adkins I, Schulz S, Borgmann S, Autenrieth IB, Gröbner S February 2008. Differential roles of Yersinia outer protein P-mediated inhibition of nuclear factor-κB in the induction of cell death in dendritic cells and macrophages. J. Med. Microbiol. 57 Pt 2: 139-44. doi:10.1099/jmm.0.47437-0. PMID 18201977. ^ Sheikh MS, Huang Y 2003. Death receptor activation complexes: it takes two to activate TNF receptor 1. Cell Cycle 2 6: 550-2. PMID 14504472. ^ Escárcega RO, Fuentes-Alexandro S, García-Carrasco M, Gatica A, Zamora A 2007. The transcription factor nuclear factor-κB and cancer. Clinical Oncology Royal College of Radiologists Great Britain 19 2: 154-61. doi:10.1016/j.clon.2006.11.013. PMID 17355113. ^ US6,410,516 PDF version 2002-06-25 Baltimore D; Sen R; Sharp PA; Singh H; Staudt L; Lebowitz JH; Baldwin Jr AS; Clerc RG; Corcoran LM; Baeuerle PA; Lenardo MJ; Fan C-M; Maniatis TPD Nuclear factors associated with transcriptional regulation ^ Karin M March 2008. The IκB kinase - a bridge between inflammation and cancer. Cell Res. 18 3: 334-42. doi:10.1038/cr.2008.30. PMID 18301380. ^ Pikarsky E, Ben-Neriah Y April 2006. NF-κB inhibition: a double-edged sword in cancer?. Eur. J. Cancer 42 6: 779-84. doi:10.1016/j.ejca.2006.01.011. PMID 16530406. ^ Mantovani A, Marchesi F, Portal C, Allavena P, Sica A 2008. Linking inflammation reactions to cancer: novel targets for therapeutic strategies. Adv. Exp. Med. Biol. 610: 112-27. PMID 18593019. ^ Vlahopoulos S, Boldogh I, Casola A, Brasier AR September 1999. Nuclear factor-κB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. Blood 94 6: 1878-89. PMID 10477716. ^ Cvek B, Dvorak Z 2007. Targeting of nuclear factor-κB and proteasome by dithiocarbamate complexes with metals. Curr. Pharm. Des. 13 30: 3155-67. doi:10.2174/138161207782110390. PMID 17979756. ^ Livolsi A, Busuttil V, Imbert V, Abraham RT, Peyron JF March 2001. Tyrosine phosphorylation-dependent activation of NF-κB. Requirement for p56 LCK and ZAP-70 protein tyrosine kinases. Eur. J. Biochem. 268 5: 1508-15. doi:10.1046/j.1432-1327.2001.02028.x. PMID 11231305. ^ Waterhouse RM, Kriventseva EV, Meister S, Xi Z, Alvarez KS, Bartholomay LC, Barillas-Mury C, Bian G, Blandin S, Christensen BM, Dong Y, Jiang H, Kanost MR, Koutsos AC, Levashina EA, Li J, Ligoxygakis P, Maccallum RM, Mayhew GF, Mendes A, Michel K, Osta MA, Paskewitz S, Shin SW, Vlachou D, Wang L, Wei W, Zheng L, Zou Z, Severson DW, Raikhel AS, Kafatos FC, Dimopoulos G, Zdobnov EM, Christophides GK 2007. Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science 316 5832: 1738-43. doi:10.1126/science.1139862. PMID 17588928. External links MeSH NF-kappa+B Sankar Ghosh 2006. Handbook of Transcription Factor NF-κB. Boca Raton: CRC. ISBN 0-8493-2794-6. Thomas D Gilmore. The Rel/NF-κB Signal Transduction Pathway. Boston University. Retrieved on 2007-12-02. v d e Transcription factors and intracellular receptors 1 Basic domains 1.1 Basic leucine zipper bZIP Activating transcription factor AATF, 1, 2, 3, 4, 5, 6, 7 AP-1 c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND BACH 1, 2 BATF BLZF1 C/EBP α, β, γ, δ, ε, ζ CREB 1, 3, L1 CREM DBP DDIT3 GABPA HLF MAF B, F, G, K NFE 2, L1, L2 NRL NRF1 XBP1 1.2 Basic helix-loop-helix bHLH ATOH1 AhR AHRR ARNT ASCL1 BHLHB2 BMAL ARNTL, ARNTL2 CLOCK EPAS1 HAND 1, 2 HES 5, 6 HEY 1, 2, L HES1 HIF 1A, 3A ID 1, 2, 3, 4 LYL1 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD, Myogenin, MYF5, MYF6 Neurogenins NeuroD 1, 2 NPAS 1, 2, 3 OLIG 1, 2 Scleraxis TAL1 Twist USF1 1.3 bHLH-ZIP AP-4 MAX MITF MNT MLX MXI1 Myc SREBP 1, 2 1.4 NF-1 NFIC 1.5 RF-X NFX1 1.6 Basic helix-span-helix bHSH AP-2 α, β, γ, δ, ε 2 Zinc finger DNA-binding domains 2.1 Nuclear receptor Cys4 subfamily 1 Thyroid hormone α, β, CAR, FXR, LXR α, β, PPAR α, β/δ, γ, PXR, RAR α, β, γ, ROR α, β, γ, Rev-ErbA α, β, VDR subfamily 2 COUP-TF I, II, Ear-2, HNF4 α, γ, PNR, RXR α, β, γ, Testicular receptor 2, 4, TLX subfamily 3 Steroid hormone Androgen, Estrogen α, β, Glucocorticoid, Mineralocorticoid, Progesterone, Estrogen related α, β, γ subfamily 4 NUR NGFIB, NOR1, NURR1 subfamily 5 LRH-1, SF1 subfamily 6 GCNF subfamily 0 DAX1, SHP 2.2 Other Cys4 GATA 1, 2, 3, 4, 5, 6 MTA 1, 2, 3 2.3 Cys2His2 General transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF 1, 2, TFIIH 1, 2, 4, 2I, 3A, 3C1, 3C2 ATBF1 BCL 6, 11A, 11B CTCF E4F1 EGR 2, 3 ERV3 GFI1 GLI-Krüppel family 1, 2, 3, YY1 HIC 1, 2 HIVEP 1, 2, 3 IKZF 1, 2, 3 ILF 2, 3 KLF 2, 4, 5, 6, 9, 10, 11, 12, 13 MTF1 MYT1 OSR1 SP 1, 2, 4, 7 Zbtb7 7A, 7B ZBTB 16, 17, 20, 32, 33, 40 zinc finger 3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 649, 655 2.4 Cys6 HIVEP1 2.5 Alternating composition AIRE DIDO1 GRLF1 ING 1, 2, 4 JARID 1A, 1B, 1C, 1D, 2 JMJD1B 3 Helix-turn-helix domains 3.1 Homeo domain ARX CDX 1, 2 CRX CUTL1 DLX 3, 4, 5 EMX2 EN 1, 2 FHL 1, 2, 3 HESX1 HHEX HLX Homeobox A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13 HOPX MEIS 1, 2 MEOX2 MNX1 MSX 1, 2 NANOG NKX 2-1, 2-2, 2-3, 2-5, 3-1, 3-2 PBX 1, 2, 3 PHF 1, 3, 6, 8, 10, 16, 17, 20, 21A PITX 1, 2, 3 POU domain PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11 OTX 1, 2 PDX1 3.2 Paired box PAX 1, 2, 3, 4, 5, 6, 7, 8, 9 3.3 Fork head / winged helix E2F 1, 2, 3, 4, 5 FOX proteins C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, O3A, O4, P1, P2, P3 3.4 Heat Shock Factors HSF 1, 2, 4 3.5 Tryptophan clusters ELF 4, 5 EGF ELK 1, 3, 4 ERF ERG ETS 1, 2, SPIB ETV 1, 4, 5, 6 FLI1 Interferon regulatory factors 1, 2, 3, 4, 5, 6, 7, 8 MYB MYBL2 3.6 TEA domain transcriptional enhancer factor 1, 2 4 β-Scaffold factors with minor groove contacts 4.1 Rel homology region NF-κB NFKB1, NFKB2, REL, RELA, RELB NFAT C1, C2, C3, C4, 5 4.2 STAT STAT 1, 2, 3, 4, 5, 6 4.3 p53 p53 TBX 1, 2, 3, 5, 19, 21, 22 4.4 MADS box Mef2 A, B, C, D SRF 4.6 TATA binding proteins TBP TBPL1 4.7 High mobility group HMGB 1, 2, 3 HNF 1A, 1B LEF1 SOX 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21 SRY SSRP1 TOX 1, 4 4.10 Cold-shock domain CSDA, YBX1 4.11 Runt CBF CBFA2T2, CBFA2T3, RUNX1, RUNX2, RUNX3, RUNX1T1 0 Other transcription factors 0.2 HMGIY HMGA 1, 2 HBP1 0.3 Pocket domain Rb RBL1 RBL2 0.5 AP-2/EREBP-related factors Apetala 2 EREBP B3 0.6 Miscellaneous ARID 1A, 1B, 2, 3A, 3B, 4A CAP IFI 16, 35 MLL 2, 3, T1 MNDA NFI A, B, C, X NFY A, B, C Rho/Sigma R-SMAD Retrieved from http://en..org/wiki/NF-%CE%BAB Categories: Genes on chromosome 4 | Genes on chromosome 10 | Genes on chromosome 11 | Genes on chromosome 19 | Genes on chromosome 2 | Programmed cell death | Transcription factorsHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Français Italiano 日本語 Português Tiếng Việt This page was last modified on 25 August 2008, at 22:1
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Effects of MonaVie Active on Antioxidant Capacity in Humans
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So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.