| First Author | Etemadi N | Year | 2013 |
| Journal | FEBS J | Volume | 280 |
| Issue | 21 | Pages | 5283-97 |
| PubMed ID | 23815148 | Mgi Jnum | J:216562 |
| Mgi Id | MGI:5608984 | Doi | 10.1111/febs.12419 |
| Citation | Etemadi N, et al. (2013) Lymphotoxin alpha induces apoptosis, necroptosis and inflammatory signals with the same potency as tumour necrosis factor. FEBS J 280(21):5283-97 |
| abstractText | Both of the TNF superfamily ligands, TNF and LTalpha, can bind and signal through TNFR1 and TNFR2, yet mice mutant for each have different phenotypes. Part of this difference is because LTalpha but not TNF can activate Herpes Virus Entry Mediator and also heterotrimerise with LTbeta to activate LTbetaR, which is consistent with the similar phenotypes of the LTalpha and LTbetaR deficient mice. However, it has also been reported that the LTalpha3 homotrimer signals differently than TNF through TNFR1, and has unique roles in initiation and exacerbation of some inflammatory diseases. Our modeling of the TNF/TNFR1 interface compared to the LTalpha3/TNFR1 structure revealed some differences that could affect signalling by the two ligands. To determine whether there were any functional differences in the ability of TNF and LTalpha3 to induce TNFR1-dependent apoptosis or necroptosis, and if there were different requirements for cIAPs and Sharpin to transmit the TNFR1 signal, we compared the ability of cells to respond to TNF and LTalpha3. Contrary to our hypothesis, we were unable to discover differences in signalling by TNFR1 in response to TNF and LTalpha3. Our results imply that the reasons for the conservation of LTalpha are most likely due either to differential regulation, the ability to signal through Herpes Virus Entry Mediator or the ability of LTalpha to form heterotrimers with LTbeta. |
