Tumorski faktor nekroze

TNF
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1A8M, 1TNF, 2AZ5, 2E7A, 2TUN, 2ZJC, 2ZPX, 3ALQ, 3IT8, 3L9J, 3WD5, 4G3Y, 4TSV, 4TWT, 5TSW
Identifikatori
Aliasi	TNF
Vanjski ID-jevi	OMIM: 191160 MGI: 104798 HomoloGene: 496 GeneCards: TNF
Lokacija gena (čovjek) Hrom. Hromosom 6 (čovjek)[1] Bend 6p21.33 Početak 31,575,565 bp[1] Kraj 31,578,336 bp[1]
Lokacija gena (miš) Hrom. Hromosom 17 (miš)[2] Bend 17 B1|17 18.59 cM Početak 35,418,357 bp[2] Kraj 35,420,983 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • protease binding • tumor necrosis factor receptor binding • cytokine activity • vezivanje identičnih proteina Ćelijska komponenta • membrana • cell surface • integral component of membrane • reciklirajući endosom • intracellular anatomical structure • integral component of plasma membrane • phagocytic cup • external side of plasma membrane • extracellular region • ćelijska membrana • Lipidni splav • Vanćelijsko Biološki proces • regulation of protein phosphorylation • positive regulation of protein phosphorylation • positive regulation of MAP kinase activity • response to salt stress • positive regulation of calcidiol 1-monooxygenase activity • positive regulation of programmed cell death • positive regulation of JNK cascade • response to organic substance • negative regulation of osteoblast differentiation • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • negative regulation of viral genome replication • humoral immune response • positive regulation of interleukin-8 production • intrinsic apoptotic signaling pathway in response to DNA damage • positive regulation of protein localization to cell surface • positive regulation of ERK1 and ERK2 cascade • glucose metabolic process • animal organ morphogenesis • apoptotic signaling pathway • negative regulation of alkaline phosphatase activity • regulation of I-kappaB kinase/NF-kappaB signaling • GO:0051637 defense response to Gram-positive bacterium • regulation of branching involved in salivary gland morphogenesis • positive regulation of phagocytosis • negative regulation of fat cell differentiation • negative regulation of myoblast differentiation • positive regulation of protein kinase B signaling • regulation of insulin secretion • osteoclast differentiation • regulation of tumor necrosis factor-mediated signaling pathway • response to virus • positive regulation of osteoclast differentiation • GO:0002719 negative regulation of cytokine production involved in immune response • positive regulation of peptidyl-serine phosphorylation • negative regulation of branching involved in lung morphogenesis • JNK cascade • death-inducing signaling complex assembly • regulation of osteoclast differentiation • defense response to bacterium • positive regulation of interleukin-6 production • I-kappaB kinase/NF-kappaB signaling • positive regulation of translational initiation by iron • sequestering of triglyceride • positive regulation of chronic inflammatory response to antigenic stimulus • positive regulation of chemokine (C-X-C motif) ligand 2 production • positive regulation of JUN kinase activity • positive regulation of hair follicle development • chronic inflammatory response to antigenic stimulus • GO:1904579 cellular response to organic cyclic compound • positive regulation of fever generation • extracellular matrix organization • positive regulation of DNA-binding transcription factor activity • cellular response to nicotine • positive regulation of podosome assembly • GO:1904489 regulation of reactive oxygen species metabolic process • positive regulation of protein transport • negative regulation of glucose import • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • leukocyte tethering or rolling • positive regulation of chemokine production • cellular extravasation • negative regulation of lipid storage • negative regulation of myosin-light-chain-phosphatase activity • GO:0045996 negative regulation of transcription, DNA-templated • GO:0033109 cortical actin cytoskeleton organization • embryonic digestive tract development • leukocyte migration • lipopolysaccharide-mediated signaling pathway • positive regulation of smooth muscle cell proliferation • positive regulation of protein kinase activity • positive regulation of superoxide dismutase activity • defense response • positive regulation of ceramide biosynthetic process • positive regulation of protein-containing complex assembly • protein kinase B signaling • GO:0032737 positive regulation of cytokine production • epithelial cell proliferation involved in salivary gland morphogenesis • positive regulation of nitric oxide biosynthetic process • negative regulation of interleukin-6 production • positive regulation of membrane protein ectodomain proteolysis • positive regulation of humoral immune response mediated by circulating immunoglobulin • positive regulation of interferon-gamma production • response to glucocorticoid • positive regulation of vitamin D biosynthetic process • positive regulation of mononuclear cell migration • MAPK cascade • negative regulation of protein-containing complex disassembly • multicellular organism development • negative regulation of bicellular tight junction assembly • positive regulation of protein-containing complex disassembly • regulation of cell population proliferation • cellular response to amino acid stimulus • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • cellular response to lipopolysaccharide • negative regulation of lipid catabolic process • regulation of establishment of endothelial barrier • positive regulation of cell adhesion • regulation of protein secretion • positive regulation of apoptotic process • inflammatory response • activation of cysteine-type endopeptidase activity involved in apoptotic process • tumor necrosis factor-mediated signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB signaling • necroptotic signaling pathway • GO:1901313 positive regulation of gene expression • extrinsic apoptotic signaling pathway • extrinsic apoptotic signaling pathway via death domain receptors • GO:1901227 negative regulation of transcription by RNA polymerase II • positive regulation of NF-kappaB transcription factor activity • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • positive regulation of leukocyte adhesion to arterial endothelial cell • positive regulation of leukocyte adhesion to vascular endothelial cell • positive regulation of blood microparticle formation • negative regulation of endothelial cell proliferation • positive regulation of heterotypic cell-cell adhesion • negative regulation of mitotic cell cycle • endothelial cell apoptotic process • positive regulation of vascular associated smooth muscle cell proliferation • negative regulation of gene expression • protein localization to plasma membrane • GO:1903364 positive regulation of protein catabolic process • regulation of signaling receptor activity • regulation of inflammatory response • cytokine-mediated signaling pathway • positive regulation of calcineurin-NFAT signaling cascade • positive regulation of NIK/NF-kappaB signaling Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	7124	21926
Ensembl	ENSG00000228978 ENSG00000230108 ENSG00000223952 ENSG00000204490 ENSG00000228321 ENSG00000232810 ENSG00000228849 ENSG00000206439	ENSMUSG00000024401
UniProt	P01375	P06804
RefSeq (mRNK)	NM_000594	NM_001278601 NM_013693
RefSeq (bjelančevina)	NP_000585	NP_001265530 NP_038721
Lokacija (UCSC)	Chr 6: 31.58 – 31.58 Mb	Chr 17: 35.42 – 35.42 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Tumorski faktor nekroze (TNF, kaheksin ili kahektin, zvani i tumorski faktor nekroze alfa ili TNF-α) citokinski mali protein koji koristi imunski sistem za ćelijsku signalizaciju. Ako makrofazi (određena bijela krvna zrnca) otkriju infekciju, oslobađaju TNF, kako bi upozorili druge ćelije imunskog sistema kao dio upalnog odgovora. TNF je član superporodica TNF, koja se sastoji od različitih transmembranskih proteina s homolognim domenom TNF.

TNF signalizacija javlja se putem dva receptora: TNFR1 i TNFR2.^[5][6] TNFR1 je konstitutivno eksprimiran na većini tipova ćelija, dok je TNFR2 ograničen prvenstveno na endotelne, epitelne i podskupine imunskih ćelija.^[5][6] Signalizacija TNF1 ima tendenciju da bude proupalna i apoptotska, dok je signalizacija TNFR2 protivupalna i podstiče ćelijsku proliferaciju.^[5][6] Suzbijanje signalizacije TNFR1 bilo je važno za liječenje autoimunske bolesti,^[7] dok signalizacija TNFR2 podstiče zacjeljivanje rana.^[6]

TNF-α postoji kao transmembranski oblik (mTNF-α) i kao topljivi oblik (sTNF-α). sTNF-α je rezultat enzimskog cijepanja mTNF-α.^[8] mTNF-α se uglavnom nalazi na monocitima/makrofazima, gdje stupa u interakciju s tkivnim receptorima, dodirom ćelija na ćeliju.^[8] sTNF-α se selektivno veže za TNFR1, dok se mTNF-α veže i za TNFR1 i za TNFR2.^[9] Vezivanje TNF-α za TNFR1 je ireverzibilno, dok je vezivanje za TNFR2 reverzibilno.^[10]

Primarna uloga TNF-a je u regulaciji imunskih ćelija. TNF, kao endogeni pirogen, može izazvati groznicu, apoptotsku ćelijsku smrt, kaheksiju, upalu i inhibirati tumorigenezu, replikaciju virusa, a i reagiraju na sepsu putem ćelijskih IL-1 i IL-6. Disregulacija proizvodnje TNF-a uključena je u različite ljudske bolesti, uključujući Alzheimerovu,^[11] kancer,^[12] glavnu depresiju,^[13] psorijazu^[14] i upalnu bolest crijeva (IBD).^[15] Iako kontroverzne, neke studije povezuju depresiju i IBD s povećanim nivoom TNF -a.^[16][17]

Pod imenom tasonermin, TNF se koristi kao imunostimulacijski lijek u liječenju određenih karcinoma. Lijekovi koji se suprotstavljaju djelovanju TNF-a koriste se u liječenju različitih upalnih bolesti, naprimjer reumatoidnog artritisa.

Određeni karcinomi mogu uzrokovati hiperprodukciju TNF-a. TNFsu paralele paratireoidnih hormona i u izazivanju sekundarne hiperkalcemije i u raku s kojim je povezana prekomerna proizvodnja.

1. ^ ^{a b c} ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 GRCh38: Ensembl release 89: ENSG00000228978, ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 - Ensembl, maj 2017
2. ^ ^{a b c} GRCm38: Ensembl release 89: ENSMUSG00000024401 - Ensembl, maj 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ ^{a b c} Heir R, Stellwagen D (2020). "TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models". Frontiers in Cellular Neuroscience. 14: 565841. doi:10.3389/fncel.2020.565841. PMC 7556297. PMID 33192311.
6. ^ ^{a b c d} Gough P, Myles IA (2020). "Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects". Frontiers in Immunology. 11: 585880. doi:10.3389/fimmu.2020.585880. PMC 7723893. PMID 33324405.
7. ^ Rolski F, Błyszczuk P (2020). "Complexity of TNF-α Signaling in Heart Disease". Journal of Clinical Medicine. 9 (10): 3267. doi:10.3390/jcm9103267. PMC 7601316. PMID 33053859.
8. ^ ^{a b} Probert L (2017). "Forward and Reverse Signaling Mediated by Transmembrane Tumor Necrosis Factor-Alpha and TNF Receptor 2: Potential Roles in an Immunosuppressive Tumor Microenvironment". Frontiers in Immunology. 8: 1675. doi:10.3389/fimmu.2017.01675. PMC 5712345. PMID 29234328.
9. ^ Rolski F, Błyszczuk P (2015). "TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects". Neuroscience. 302: 2–22. doi:10.1016/j.neuroscience.2015.06.038. PMID 26117714.
10. ^ Szondy Z, Pallai A (2017). "Transmembrane TNF-alpha reverse signaling leading to TGF-beta production is selectively activated by TNF targeting molecules: Therapeutic implications". Pharmacological Research. 115: 124–132. doi:10.1016/j.phrs.2016.11.025. PMID 27888159.
11. ^ Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010). "A meta-analysis of cytokines in Alzheimer's disease". Biol Psychiatry. 68 (10): 930–941. doi:10.1016/j.biopsych.2010.06.012. PMID 20692646. S2CID 6544784.
12. ^ Locksley RM, Killeen N, Lenardo MJ (2001). "The TNF and TNF receptor superfamilies: integrating mammalian biology". Cell. 104 (4): 487–501. doi:10.1016/S0092-8674(01)00237-9. PMID 11239407. S2CID 7657797.
13. ^ Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010). "A meta-analysis of cytokines in major depression". Biol Psychiatry. 67 (5): 446–457. doi:10.1016/j.biopsych.2009.09.033. PMID 20015486. S2CID 230209.
14. ^ Victor FC, Gottlieb AB (2002). "TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis". J Drugs Dermatol. 1 (3): 264–75. PMID 12851985.
15. ^ Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002). "Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease". Gut. 51 (1): 37–43. doi:10.1136/gut.51.1.37. PMC 1773288. PMID 12077089.
16. ^ Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ (2007). "Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review". Inflammatory Bowel Diseases. 13 (2): 225–234. doi:10.1002/ibd.20062. PMID 17206706.
17. ^ Bobińska K, Gałecka E, Szemraj J, Gałecki P, Talarowska M (2017). "Is there a link between TNF gene expression and cognitive deficits in depression?". Acta Biochim. Pol. 64 (1): 65–73. doi:10.18388/abp.2016_1276. PMID 27991935.