| First Author | Klein T | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8777 | PubMed ID | 26525107 |
| Mgi Jnum | J:228041 | Mgi Id | MGI:5704287 |
| Doi | 10.1038/ncomms9777 | Citation | Klein T, et al. (2015) The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-kappaB signalling. Nat Commun 6:8777 |
| abstractText | Antigen receptor signalling activates the canonical NF-kappaB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined roles for linear ubiquitination. The paracaspase MALT1 cleaves and removes negative checkpoint proteins, amplifying lymphocyte responses in NF-kappaB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living MALT1(mut/mut) patient with healthy MALT1(+/mut) 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-kappaB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-kappaB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-kappaB pathway-first promoting activation via the CBM-then triggering HOIL1-dependent negative-feedback termination, preventing reactivation. |
