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The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-\u03baB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living\n                    <jats:italic>MALT1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>mut\/mut<\/jats:italic>\n                    <\/jats:sup>\n                    patient with healthy\n                    <jats:italic>MALT1<\/jats:italic>\n                    <jats:sup>\n                      +\/\n                      <jats:italic>mut<\/jats:italic>\n                    <\/jats:sup>\n                    family members using 10-plex Tandem Mass Tag TAILS N-terminal peptide proteomics. We identify HOIL1 of the linear ubiquitin chain assembly complex as a novel MALT1 substrate. We show linear ubiquitination at B-cell receptor microclusters and signalosomes. Late in the NF-\u03baB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-\u03baB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-\u03baB pathway\u2014first promoting activation via the CBM\u2014then triggering HOIL1-dependent negative-feedback termination, preventing reactivation.\n                  <\/jats:p>","DOI":"10.1038\/ncomms9777","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T05:16:16Z","timestamp":1446527776000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-\u03baB signalling"],"prefix":"10.1038","volume":"6","author":[{"given":"Theo","family":"Klein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Yu","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Blank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Dufour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyeong","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Bolger-Munro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Scurll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Priatel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schweigler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samu","family":"Melkko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa I.","family":"Viner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine H.","family":"R\u00e9gnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart E.","family":"Turvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Overall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,3]]},"reference":[{"key":"BFncomms9777_CR1","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nature09816","volume":"471","author":"B Gerlach","year":"2011","unstructured":"Gerlach, B. et al. 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