{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:25:32Z","timestamp":1787318732557,"version":"build-2736575974"},"reference-count":31,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["FS\/14\/29\/30896"],"award-info":[{"award-number":["FS\/14\/29\/30896"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["SP\/14\/2\/30922"],"award-info":[{"award-number":["SP\/14\/2\/30922"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MRC","award":["MR\/J007501\/1"],"award-info":[{"award-number":["MR\/J007501\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,23]]},"abstract":"<jats:p>Inhibiting MAPK14 (p38\u03b1) diminishes cardiac damage in myocardial ischemia. During myocardial ischemia, p38\u03b1 interacts with TAB1, a scaffold protein, which promotes p38\u03b1 autoactivation; active p38\u03b1 (pp38\u03b1) then transphosphorylates TAB1. Previously, we solved the X-ray structure of the p38\u03b1-TAB1 (residues 384\u2013412) complex. Here, we further characterize the interaction by solving the structure of the pp38\u03b1-TAB1 (residues 1\u2013438) complex in the active state. Based on this information, we created a global knock-in (KI) mouse with substitution of 4 residues on TAB1 that we show are required for docking onto p38\u03b1. Whereas ablating p38\u03b1 or TAB1 resulted in early embryonal lethality, the TAB1-KI mice were viable and had no appreciable alteration in their lymphocyte repertoire or myocardial transcriptional profile; nonetheless, following in vivo regional myocardial ischemia, infarction volume was significantly reduced and the transphosphorylation of TAB1 was disabled. Unexpectedly, the activation of myocardial p38\u03b1 during ischemia was only mildly attenuated in TAB1-KI hearts. We also identified a group of fragments able to disrupt the interaction between p38\u03b1 and TAB1. We conclude that the interaction between the 2 proteins can be targeted with small molecules. The data reveal that it is possible to selectively inhibit signaling downstream of p38\u03b1 to attenuate ischemic injury.<\/jats:p>","DOI":"10.1172\/jci.insight.121144","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T11:01:09Z","timestamp":1534935669000},"source":"Crossref","is-referenced-by-count":26,"title":["The TAB1-p38\u03b1 complex aggravates myocardial injury and can be targeted by small molecules"],"prefix":"10.1172","volume":"3","author":[{"given":"Gian F.","family":"De Nicola","sequence":"first","affiliation":[{"name":"British Heart Foundation Centre of Excellence, The Rayne Institute, St. Thomas\u2019 Hospital, and"},{"name":"The Randall Division, New Hunt\u2019s House, Guy\u2019s Campus, King\u2019s College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Bassi","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Excellence, The Rayne Institute, 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