TWEAK (His-FLAG-Tag)

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a type II membrane protein and a member of the TNF superfamily. The “weak” apoptotic activity as it triggers death in only limited cell types and this death is mediated via a non-death receptor, Fn14.

Interacting protein(s): Fn14
Related products: Hexa-Ligand

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Quick Spec

Description

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a type II membrane protein and a member of the TNF superfamily. The “weak” apoptotic activity as it triggers death in only limited cell types and this death is mediated via a non-death receptor, Fn14. TWEAK was initially described as a surface protein but was found can be shed into the extracellular milieu as a soluble trimeric protein.

TWEAK transcripts can be found in many tissues in abundance. The apoptotic activity of TWEAK was classically described using a human adenocarcinoma cell, HT29, in the presence of ϒ-interferon. Similar to LT-β and possibly CD30L, TWEAK triggers apoptosis via a receptor which does not contain a death domain. Tweak receptor, also called Fn14, is the second smallest member of the TNF receptor (TNFR) superfamily, and it appears to signal via recruitment of several different TNFR-associated factors.

TWEAK has multiple biological activities, including stimulation of cell growth and angiogenesis, induction of inflammatory cytokines, and under some experimental conditions, stimulation of apoptosis. An interesting fusion protein, TWE-PRIL, has been identified as an endogenous hybrid transcript between TWEAK and APRIL. TWE-PRIL is composed of the intracellular, transmembrane and stalk regions of TWEAK and APRIL’s receptor-binding domain. The functions of TWE-PRIL has not been established.

Amino Acid Sequence

References

1. Siegmund D, Zaitseva O, Wajant H. Fn14 and TNFR2 as regulators of cytotoxic TNFR1 signaling. Front Cell Dev Biol. 2023;11:1267837. Epub 20231106. doi: 10.3389/fcell.2023.1267837. PubMed PMID: 38020877; PubMed Central PMCID: PMC10657838.

2. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. Chicheportiche Y., Bourdon P.R., Xu H., Hsu Y.-M., Scott H., Hession C., Garcia I., Browning J.L. J. Biol. Chem. 272:32401-32410 (1997) 

3. An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein. Pradet-Balade B., Medema J.P., Lopez-Fraga M., Lozano J.C., Kolfschoten G.M., Picard A., Martinez-A C., Garcia-Sanz J.A., Hahne M. EMBO J. 21:5711-5720 (2002) 

4. TWEAK induces angiogenesis and proliferation of endothelial cells. Lynch C.N., Wang Y.C., Lund J.K., Chen Y.-W., Leal J.A., Wiley S.R. J. Biol. Chem. 274:8455-8459 (1999) 

5. TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor. Wiley S.R., Winkles J.A. Cytokine Growth Factor Rev. 14:241-249 (2003)