TNF-related weak inducer of apoptosis (TWEAK) signaling pathway (WP2036)

TNF related weak inducer of apoptosis (TWEAK) is a small pleiotropic cytokine of the TNF super family and its gene is located at chromosome 17p13.1. TWEAK has been reported to be expressed in tissues that include heart, brain, kidney and also in mononuclear blood cells. The multiple biological activities of TWEAK include stimulation of cell growth and angiogenesis, induction of inflammatory cytokines, and stimulation of apoptosis. It has been shown to be involved in the induction of cellular proliferation in liver cells, osteoblasts, astrocytes, synoviocytes, kidney cells and skeletal muscles. Furthermore, TWEAK plays a substantial role in cellular differentiation in osteoclasts. TWEAK induces glioma cell survival via imparting resistance to cytotoxic agents. It imparts its downstream signaling events by binding to its receptor, FGF inducible 14 protein (Fn14). Two modes of TWEAK-Fn14 (ligand-receptor) interactions have been proposed (i) the ligand dependent interaction which involves the higher concentration of homotrimeric TWEAK, that binds to low concentration of Fn14 in a heterohexameric complex (ii) ligand-independent interaction when the ligand concentration is lower than the receptor concentration which induces the ligand independent interaction. The receptors homotrimerize to activate the downstream events. The signaling cascades reported under TWEAK-Fn14 interactions are the canonical and noncanonical NF-κB pathways and the MAPK pathway. There has been a report on crosstalk between Wnt and TWEAK pathways. In myoblasts the PI3K-AKT module has been reported to be inhibited under TWEAK stimulus. AKT phosprorylation leads to the activation of GSK3β resulting in increase of phospho-GSk3β and active β-catenin1 (CTNNB1) (dephosphorylated) levels. GSK3β and β-catenin1 remain associated in the cytoplasm, phosphorylation of GSK3β leads to the dissociation of β-catenin1 (dephosphorylated) resulting in the nuclear translocation of the protein. Despite of reports on TWEAK binding to other receptors including CD163 and DR3 the downstream events following the binding is yet to be established. The data provided by us would foster enormous avenues for further studies on TWEAK associated proteins and the related disorders such as cancer and autoimmune diseases. The data would enable therapeutic studies by selecting the pathological events and the simultaneous production of blocking agents. Despite the minimal amount of data, ours can also be used in the overlay of various high throughput data enabling pathway analysis and can be accessed by any pathway resource to generate a customized pathway. Please access this pathway at [http://www.netpath.org/netslim/tweak_pathway.html NetSlim] database. If you use this pathway, please cite Bhattacharjee2012 paper (see below). Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2036 CPTAC Assay Portal].
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Authors

Khanspers, NetPath, Ddigles, MaintBot, AlexanderPico, Zari, MirellaKalafati, Evelo, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: tumor necrosis factor superfamily mediated signaling pathway

Participants

Label Type Compact Identifier
Apoptosis Pathway wikipathways:WP254
Proteosome degradation Pathway wikipathways:WP183
Protein Protein ncbigene:5894
RELB Protein ncbigene:5971
NFKB1 Protein ncbigene:4790
TRAF1 Protein ncbigene:7185
NFKB2 Protein ncbigene:4791
IKBKB Protein ncbigene:3551
IL6 Rna ncbigene:3569
MAP3K14 Protein ensembl:ENSG00000006062
TRAF3 Protein ncbigene:7187
MAPK3 Protein ncbigene:5595
HDAC1 Protein ncbigene:3065
TNFRSF12A Protein ncbigene:51330
RAC1 Protein ncbigene:5879
TNFSF12 Protein ncbigene:8742
TRAF2 Protein ncbigene:7186
BIRC2 Protein ncbigene:329
CASP8 Protein ncbigene:841
FADD Protein ncbigene:8772
MAPK1 Protein ncbigene:5594
NFKBIB Protein ncbigene:4793
RIPK1 Protein ncbigene:8737
AKT2 Protein ncbigene:208
TNFSF12 Protein ncbigene:8742
TRAF5 Protein ncbigene:7188
AKT1 Protein ncbigene:207
CHUK Protein ncbigene:1147
NFKBIA Protein ncbigene:4792
CTNNB1 Protein ncbigene:1499
CCL5 Rna ncbigene:6352
MMP9 Rna ncbigene:4318
MAP3K7 Protein ncbigene:6885
MAPK8 Protein ncbigene:5599
MAPK9 Protein ncbigene:5601
RELA Protein ncbigene:5970
GSK3B Protein ncbigene:2932
MAPK14 Protein ncbigene:1432
TNFSF12 Protein ncbigene:8742
CTNNB1 Protein ncbigene:1499
CASP3 Protein uniprot:P42574
CCL2 Rna ncbigene:6347
CCL5 Rna ncbigene:6352
NFKB1 Protein ncbigene:4790
RELA Protein ncbigene:5970
CHUK Protein ncbigene:1147
RELB Protein ncbigene:5971
NFKB2 Protein ncbigene:4791
CASP8 Protein ncbigene:841
CASP7 Protein ncbigene:840
JUN Protein ncbigene:3725
Protein Protein ncbigene:5894
TRIM63 Protein ncbigene:84676
TNF Rna ncbigene:7124
BIRC3 Protein ncbigene:330
TRAF2 Protein ncbigene:7186
TNF Protein ncbigene:7124
TNF Protein ncbigene:7124
TNFRSF1 Protein ncbigene:51330

References

  1. Bhattacharjee M, Raju R, Radhakrishnan A, Nanjappa V, Muthusamy B, Singh K, et al. A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway. J Signal Transduct. 2012;2012:376470. PubMed Europe PMC Scholia