TNFRSF12A gene

Last updated on: 01.08.2024

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Definition
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The TNFRSF12A gene (TNFRSF12A stands for TNF Receptor Superfamily Member 12A) is a protein-coding gene located on chromosome 16p13.3.

General information
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The TNFRSF12A gene codes for the TNFSF12/TWEAK receptor. This receptor protein is a weak trigger of apoptosis in some cell types. Promotes angiogenesis and proliferation of endothelial cells. Can modulate cellular adhesion to matrix proteins.

The protein receptor is involved in the positive regulation of the extrinsic apoptotic signaling pathway and the regulation of wound healing.

Diseases associated with TNFRSF12A include glioblastoma and multiple sclerosis. Related signaling pathways include Akt signaling and TNF superfamily - human ligand-receptor interactions.

Note(s)
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The TNFRSF protein Fn14 is the tumor necrosis factor-like weak apoptosis inducer (TWEAK) receptor. Fn14 has been described in fibroblasts as fibroblast growth factor-inducible-14, a gene that responds directly to growth factors. Although Fn14 is hardly expressed in healthy endothelial cells, neurons, astrocytes, microglia and progenitor cells, it is highly inducible in these cells. The interaction of TWEAK with its (Fn14) receptor triggers several molecular events and biological responses depending on the cell type and microenvironment (Bhattacharjee M et al. 2012)

These downstream signaling pathways include the large number of 46 proteins and 28 inducible genes. Accordingly, the interaction of TWEAK with its Fn14 receptor primarily activates nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) via interaction with intracellular TNF receptor-associated factors. mTWEAK appears to activate the canonical NF-κB signaling pathway more efficiently, while both membrane-bound and soluble TWEAK can induce the non-canonical NF-κB signaling pathway (Roos C et al. 2010).

Literature
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  1. Bhattacharjee M et al.(2012) A bioinformatics resource for TWEAK-Fn14 signaling pathway. J Signal Transduct:376470.
  2. Boulamery A et al. (2017) Regulation of Neuroinflammation: What Role for the Tumor Necrosis Factor-Like Weak Inducer of Apoptosis/Fn14 Pathway? Front Immunol 8:1534.
  3. Desplat-Jégo S et al. (2009) TWEAK is expressed at the cell surface of monocytes during multiple sclerosis. J Leukoc Biol 85:132-135.).
  4. Maecker H et al. (2005) TWEAK attenuates the transition from innate to adaptive immunity. Cell 123: 931-944)
  5. Nakayama M et al.(2000) Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity. J Exp Med 192:1373-1380.
  6. Roos C et al. (2010) Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway. J Immunol 185:1593-1605.
  7. Rousselet E et al. (2012) Tumor necrosis factor-like weak inducer of apoptosis induces astrocyte proliferation through the activation of transforming-growth factor-α/epidermal growth factor receptor signaling pathway. Mol Pharmacol 82:948-957.
  8. Wicovsky A et al. (2009) TNF-like weak inducer of apoptosis inhibits proinflammatory TNF receptor-1 signaling. Cell Death Differ 16:1445-1459)

Last updated on: 01.08.2024