The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation
- PMID:12529173
- PMCID: PMC1223299
- DOI: 10.1042/BJ20021730
The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation
Abstract
Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein. The human Fn14 protein was recently identified as a cell-surface receptor for the tumour necrosis factor (TNF) superfamily member named TWEAK (TNF-like weak inducer of apoptosis). In the present paper, we report that the human TWEAK extracellular domain can also bind the murine Fn14 protein. Furthermore, site-specific mutagenesis and directed yeast two-hybrid interaction assays revealed that the TNFR-associated factor (TRAF) 1, 2, 3 and 5 adaptor molecules bind the murine Fn14 cytoplasmic tail at an overlapping, but non-identical, amino acid sequence motif. We also found that TWEAK treatment of quiescent NIH 3T3 cells stimulates inhibitory kappaBalpha phosphorylation and transcriptional activation of a nuclear factor-kappaB (NF-kappaB) enhancer/luciferase reporter construct. Fn14 overexpression in transiently transfected NIH 3T3 cells also promotes NF-kappaB activation, and this cellular response requires an intact TRAF binding site. These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway.
Similar articles
- The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily.Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC.Galibert L, et al.J Biol Chem. 1998 Dec 18;273(51):34120-7. doi: 10.1074/jbc.273.51.34120.J Biol Chem. 1998.PMID:9852070
- TWEAK-independent Fn14 self-association and NF-κB activation is mediated by the C-terminal region of the Fn14 cytoplasmic domain.Brown SA, Cheng E, Williams MS, Winkles JA.Brown SA, et al.PLoS One. 2013 Jun 4;8(6):e65248. doi: 10.1371/journal.pone.0065248. Print 2013.PLoS One. 2013.PMID:23750247Free PMC article.
- The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor-inducible 14 (Fn14) signaling system regulates glioma cell survival via NFkappaB pathway activation and BCL-XL/BCL-W expression.Tran NL, McDonough WS, Savitch BA, Sawyer TF, Winkles JA, Berens ME.Tran NL, et al.J Biol Chem. 2005 Feb 4;280(5):3483-92. doi: 10.1074/jbc.M409906200. Epub 2004 Dec 16.J Biol Chem. 2005.PMID:15611130
- TWEAK and Fn14: new molecular targets for cancer therapy?Winkles JA, Tran NL, Berens ME.Winkles JA, et al.Cancer Lett. 2006 Apr 8;235(1):11-7. doi: 10.1016/j.canlet.2005.03.048.Cancer Lett. 2006.PMID:15885893Review.
- Role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in rheumatic diseases.Zhu LX, Zhang HH, Mei YF, Zhao YP, Zhang ZY.Zhu LX, et al.Chin Med J (Engl). 2012 Nov;125(21):3898-904.Chin Med J (Engl). 2012.PMID:23106895Review.
Cited by
- CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury.Akahori H, Karmali V, Polavarapu R, Lyle AN, Weiss D, Shin E, Husain A, Naqvi N, Van Dam R, Habib A, Choi CU, King AL, Pachura K, Taylor WR, Lefer DJ, Finn AV.Akahori H, et al.Nat Commun. 2015 Aug 5;6:7792. doi: 10.1038/ncomms8792.Nat Commun. 2015.PMID:26242746Free PMC article.
- The HER2- and heregulin β1 (HRG)-inducible TNFR superfamily member Fn14 promotes HRG-driven breast cancer cell migration, invasion, and MMP9 expression.Asrani K, Keri RA, Galisteo R, Brown SA, Morgan SJ, Ghosh A, Tran NL, Winkles JA.Asrani K, et al.Mol Cancer Res. 2013 Apr;11(4):393-404. doi: 10.1158/1541-7786.MCR-12-0542. Epub 2013 Feb 1.Mol Cancer Res. 2013.PMID:23378579Free PMC article.
- NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients.Liu JY, Jiang L, He T, Liu JJ, Fan JY, Xu XH, Tang B, Shi Y, Zhao YL, Qian F, Wang Y, Cui YH, Yu PW.Liu JY, et al.Cell Death Dis. 2019 Feb 15;10(3):162. doi: 10.1038/s41419-019-1388-5.Cell Death Dis. 2019.PMID:30770791Free PMC article.
- TRAF2 and cIAP2 involve in TWEAK-induced MMP-9 production in fibroblast-like synoviocytes.Xia L, Shen H, Lu J, Xiao W.Xia L, et al.Rheumatol Int. 2012 Jan;32(1):281-2. doi: 10.1007/s00296-010-1640-x. Epub 2011 Jan 13.Rheumatol Int. 2012.PMID:21229359No abstract available.
- TWEAK and Fn14 in the Neurovascular Unit.Yepes M.Yepes M.Front Immunol. 2013 Nov 11;4:367. doi: 10.3389/fimmu.2013.00367. eCollection 2013.Front Immunol. 2013.PMID:24273541Free PMC article.Review.
References
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases