The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling

Theo Klein, Shan-Yu Fung, Florian Renner, Michael A. Blank, Antoine Dufour, Sohyeong Kang, Madison Bolger-Munro, Joshua M. Scurll, John J. Priatel, Patrick Schweigler, Samu Melkko, Michael R. Gold, Rosa I. Viner, Catherine H. Régnier (), Stuart E. Turvey () and Christopher M. Overall ()
Additional contact information
Theo Klein: University of British Columbia
Shan-Yu Fung: University of British Columbia
Florian Renner: Novartis Institutes for BioMedical Research, Novartis Campus
Michael A. Blank: Thermo Fisher Scientific
Antoine Dufour: University of British Columbia
Sohyeong Kang: Child & Family Research Institute, BC Children’s Hospital
Madison Bolger-Munro: University of British Columbia
Joshua M. Scurll: University of British Columbia
John J. Priatel: Child & Family Research Institute, BC Children’s Hospital
Patrick Schweigler: Novartis Institutes for BioMedical Research, Novartis Campus
Samu Melkko: Novartis Institutes for BioMedical Research, Novartis Campus
Michael R. Gold: University of British Columbia
Rosa I. Viner: Thermo Fisher Scientific
Catherine H. Régnier: Novartis Institutes for BioMedical Research, Novartis Campus
Stuart E. Turvey: University of British Columbia
Christopher M. Overall: University of British Columbia

Nature Communications, 2015, vol. 6, issue 1, 1-17

Abstract: Abstract Antigen receptor signalling activates the canonical NF-κB 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-κB activation and in B-cell lymphoma subtypes. To identify new human MALT1 substrates, we compare B cells from the only known living MALT1mut/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-κB activation cycle HOIL1 cleavage transiently reduces linear ubiquitination, including of NEMO and RIP1, dampening NF-κB activation and preventing reactivation. By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regulator of the human canonical NF-κB pathway—first promoting activation via the CBM—then triggering HOIL1-dependent negative-feedback termination, preventing reactivation.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9777 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9777

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9777

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().