@article{KuckaLangZhangetal.2021, author = {Kucka, Kirstin and Lang, Isabell and Zhang, Tengyu and Siegmund, Daniela and Medler, Juliane and Wajant, Harald}, title = {Membrane lymphotoxin-α\(_2\)β is a novel tumor necrosis factor (TNF) receptor 2 (TNFR2) agonist}, series = {Cell Death \& Disease}, volume = {12}, journal = {Cell Death \& Disease}, number = {4}, doi = {10.1038/s41419-021-03633-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260077}, pages = {360}, year = {2021}, abstract = {In the early 1990s, it has been described that LTα and LTβ form LTα\(_2\)β and LTαβ\(_2\) heterotrimers, which bind to TNFR1 and LTβR, respectively. Afterwards, the LTαβ\(_2\)-LTβR system has been intensively studied while the LTα\(_2\)β-TNFR1 interaction has been ignored to date, presumably due to the fact that at the time of identification of the LTα\(_2\)β-TNFR1 interaction one knew already two ligands for TNFR1, namely TNF and LTα. Here, we show that LTα\(_2\)β interacts not only with TNFR1 but also with TNFR2. We furthermore demonstrate that membrane-bound LTα\(_2\)β (memLTα\(_2\)β), despite its asymmetric structure, stimulates TNFR1 and TNFR2 signaling. Not surprising in view of its ability to interact with TNFR2, LTα\(_2\)β is inhibited by Etanercept, which is approved for the treatment of rheumatoid arthritis and also inhibits TNF and LTα.}, language = {en} }