TNF

Protein TNF

Identifiers
HUGO:TNF
tumor necrosis factor
HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375
TNFA, "tumor necrosis factor (TNF superfamily, member 2)"
HUGO:TNF HGNC:11892 ENTREZ:7124 UNIPROT:P01375

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / INFLAMMATORY_SIGNALING_PATHWAYS
Cancer Associated Fibroblasts / CYTOKINES_CHEMOKINES_PRODUCTION
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
EMT Senescence / SENESCENCE
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / TNF_RESPONSE
Regulated Cell Death / ER_STRESS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_EXPRESSION

References
PMID:21411734 PMID:20038811
PMID:23769623
TNF is one of key CAF activating agents
PMID:17916596
In vitro analyses
revealed a striking induction of IL-8 expression in CAFs
and LFs by tumor necrosis factor-alpha (TNFA). The effect
of TNFA on CAFs is inhibited by the nuclear factor-kB
inhibitor parthenolide.
PMID:8910423
both TNFR1 and TNFR2 receptors play role in TNF signal transduction in mouse fibroblasts
Tnfr1 is essential in mediating proliferative signals
Tnfr1 Exclusively Activates Transcription Factor NF-??B in Mouse Fibroblasts
Ap-1 was independently activated through both Tnf receptors, probably via prolonged activation of the c-Jun kinase
Tnfr1 and Tnfr2 Control Erk1 and Erk2 Kinase Activity
Tnfr1 and Tnfr2 Control activation of RPS6KA1
Raf-1, Mek-1, and Mekk responded with enhanced kinase activity to Tnf treatment in all wt, tnfr1o, and tnfr2o fibroblasts, supporting again that both Tnf receptors individually are signaling-competent. The activation factors were about 1.5-4 for Raf-1, Mekk, and Mek-1 in wt, tnfr1o, and tnfr2o fibroblasts (Table II). Interestingly, Raf-B, an isoform of c-Raf-1 reported to be mainly localized to the brain (64, 65, 66), also responded to Tnf treatment of the fibroblasts.
PMID:11112697
TNF-(alpha) substantially promoted activation of pro-MMP-2 in dermal fibroblasts embedded in type-I collagen. In marked contrast, collagen or TNF-(alpha) individually had little influence on the fibroblast-mediated pro-MMP-2 activation. One well-characterized mechanism for pro-MMP-2 activation is through a membrane type matrix metalloproteinase, such as MT1-MMP. We report that TNF-(alpha) significantly induced MT1-MMP at the mRNA and protein levels when the dermal fibroblasts were grown in collagen. Although the intracellular signaling pathway regulating mt1-mmp gene expression is still obscure, both TNF-(alpha) and collagen activate the NF-(kappa)B pathway. In this report we provide three sets of evidence to support a hypothesis that activation of NF-(kappa)B is essential to induce MT1-MMP expression in fibroblasts after TNF-(alpha) exposure. First, SN50, a peptide inhibitor for NF-(kappa)B nuclear translocation, simultaneously blocked the TNF-(alpha) and collagen mediated MT1-MMP induction and pro-MMP-2 activation.
PMID:26201938
The expression levels of cytokine genes, including those for IL6, CXCL8, TNF, TGFB1, and VEGFA, were higher in CAFs. T cell proliferation was suppressed more by CAFs or their supernatants than by NFs.
PMID:20184663
PMID:23567181
Tumor necrosis factor (TNF) and IL6 were shown to be a potent mast cell chemoattractant. TNF induced a strong, dose-dependent migratory response of peritoneal mast cells
PMID:19411070
TNFa dramatically enhanced the protein stabilization of Snail1 through NF-kB mediated CSN2 induction.
PMID:23430059
PMID:21133840
TNF is a pleiotropic cytokine produced by many different types of cells in the body. However, cells of the monocytic lineage???such as macrophages, astroglia, microglia, Langerhans cells, Kupffer cells, and alveolar macrophages???are the primary synthesizers of TNF
PMID:1431106
TNF induced tumoricidal activity of macrophages.
PMID:14607933,??14625680
TNF and IFNG cooperate in the activation of macrophages.
PMID:18633355
TNF is pro-angiogenic facror.
PMID:23510023, PMID:23170255
TRAIL, FASL and TNF provides Dendritic cell tumor killing activity.()??
L10 stimulates HO1 expression via MAPK p38 stimulation. HO-1 mediates IL-10-induced suppression of TNF- production and IL-10-induced suppression of MMP9 and INOS expression
PMID:22955274
SHIP inhibit MAPKp38 activation and prevent MNK1 phosphorylation by inhibiting the p38 MAPK pathway downstream of IL10. MNK1 regulates TNFa mRNA polysome assembly and upregulates TNFa translation.IL-10 Inhibits TNF Translation through SHIP1-mediated Inhibition of Mnk1
PMID:15699106, PMID:12646658
Phosphorylated STAT1 binds to TNF promoter end induces TNF expression downstream of IFNG.
PMID:15099563
Mast cells produce cytokines TNF-a, TGF-b, IFN-a, IL-1a, IL-1b, IL-5, IL-6,
IL-13, IL-16, IL-18
PMID:24092389
TANs from early tumors are more cytotoxic toward tumor cells and produce higher levels of TNF-??, NO, and H2O2 and, in established tumors, these functions are downregulated and TAN acquire a more protumorigenic phenotype
PMID:21826665
TANs produce TNF and IL1B, probably downstream of TLR4

TNF@default

References
ca_re284( Cancer Associated Fibroblasts ):
PMID:11875494
IL10-induced p38 phosphorylation.
PMID:20435894
SHIP inhibit MAPKp38 activation and prevent
MKNK1 phosphorylation by inhibiting the p38MAPK
pathway downstream of IL10.
PMID:10925299
IL13 induces p38 MAPK phosphorilation and activation, p38 MAPK participates in arginase activation??downstream of IL13.
PMID:23508573
HMGB1 induces activation (phosphorylation) of p38 via TLR4.
PMID:12811837, PMID:16713974
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
PMID:16713974
TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages.
This activation is inhibited by IFNG signaling.
PMID:11438547, PMID:24378531
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
ca_re410( Cancer Associated Fibroblasts ):
CASCADE:LIF
PMID:22595692
The structure of receptors of IL6 like cytokines

TNF@Extracellular space

References
em_emtc_emtc_re1218( EMT Senescence ):
PMID:19411070
Activation of NFKB pathway by TNFa
TNFa dramatically enhanced the protein stabilization of Snail1 through NF-kB mediated CSN2 induction.

Modifications:
In compartment: Cytosol

TNF@Cytosol

In compartment: Extracellular space

TNF@Extracellular space

In compartment: INNATE_IMMUNE_CELL_Cytosol

TNF@INNATE_IMMUNE_CELL_Cytosol

In compartment: T_cell

TNF@T_cell

In compartment: default

TNF@default

Participates in complexes:
In compartment: Cytosol

In compartment: INNATE_IMMUNE_CELL_Membrane

In compartment: TNFRSF1 Receptor Complex

TNFRSF1A|hm3:TNF|hm3@TNFRSF1 Receptor Complex

Participates in reactions:
As Reactant or Product:

As Catalyser: