{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:50:50Z","timestamp":1779349850560,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T00:00:00Z","timestamp":1438214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI045125"],"award-info":[{"award-number":["AI045125"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"Summary<\/jats:title>V<\/jats:italic><\/jats:styled-content>ibrio cholerae<\/jats:italic> uses a multiprotein transcriptional regulatory cascade to control expression of virulence factors cholera toxin and toxin\u2010co\u2010regulated pilus. Two proteins in this cascade are ToxR<\/jats:styled-content> and TcpP<\/jats:styled-content> \u2013 unusual membrane\u2010localized transcription factors with relatively undefined periplasmic domains and transcription activator cytoplasmic domains. TcpP<\/jats:styled-content> and ToxR<\/jats:styled-content> function with each other and two other membrane\u2010localized proteins, TcpH<\/jats:styled-content> and ToxS<\/jats:styled-content>, to activate transcription of toxT<\/jats:italic>, encoding the direct activator of toxin and pilus genes. Under some conditions, TcpP<\/jats:styled-content> is degraded in a two\u2010step proteolytic pathway known as regulated intramembrane proteolysis (RIP<\/jats:styled-content>), thereby inactivating the cascade. The second step in this proteolytic pathway involves the zinc metalloprotease YaeL<\/jats:styled-content>; V<\/jats:italic><\/jats:styled-content>.\u2009cholerae<\/jats:italic> cells lacking YaeL<\/jats:styled-content> accumulate a truncated yet active form of TcpP<\/jats:styled-content> termed TcpP<\/jats:styled-content>*. We hypothesized that a protease acting prior to YaeL<\/jats:styled-content> degrades TcpP<\/jats:styled-content> to TcpP<\/jats:styled-content>*, which is the substrate of YaeL<\/jats:styled-content>. In this study, we demonstrate that a C<\/jats:styled-content>\u2010terminal protease called T<\/jats:styled-content>sp degrades TcpP<\/jats:styled-content> to form TcpP<\/jats:styled-content>*, which is then acted upon by YaeL<\/jats:styled-content>. We present evidence that TcpH<\/jats:styled-content> and T<\/jats:styled-content>sp serve to protect full\u2010length TcpP<\/jats:styled-content> from spurious proteolysis by YaeL<\/jats:styled-content>. Cleavage by T<\/jats:styled-content>sp occurs in the periplasmic domain of TcpP<\/jats:styled-content> and requires residues TcpPA<\/jats:styled-content>172 and TcpPI<\/jats:styled-content>174 for wild\u2010type activity.<\/jats:p>","DOI":"10.1111\/mmi.13069","type":"journal-article","created":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T06:29:39Z","timestamp":1432276179000},"page":"822-831","source":"Crossref","is-referenced-by-count":32,"title":["Regulated intramembrane proteolysis of the virulence activator TcpP<\/scp> in V<\/i><\/scp>ibrio cholerae<\/i> is initiated by the tail\u2010specific protease (T<\/scp>sp)"],"prefix":"10.1111","volume":"97","author":[{"given":"Wei Ping","family":"Teoh","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Ann Arbor MI 48109 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyl S.","family":"Matson","sequence":"additional","affiliation":[{"name":"Department of 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