Serine 165 phosphorylation of SHARPIN regulates the activation of NF-κB.
Cell Biology
Immunology
Molecular Biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Jan 2021
22 Jan 2021
Historique:
received:
20
07
2020
revised:
27
10
2020
accepted:
09
12
2020
entrez:
4
1
2021
pubmed:
5
1
2021
medline:
5
1
2021
Statut:
epublish
Résumé
The adaptor SHARPIN composes, together with the E3 ligases HOIP and HOIL1, the linear ubiquitin chain assembly complex (LUBAC). This enzymatic complex catalyzes and stamps atypical linear ubiquitin chains onto substrates to modify their fate and has been linked to the regulation of the NF-κB pathway downstream of most immunoreceptors, inflammation, and cell death. However, how this signaling complex is regulated is not fully understood. Here, we report that a portion of SHARPIN is constitutively phosphorylated on the serine at position 165 in lymphoblastoid cells and can be further induced following T cell receptor stimulation. Analysis of a phosphorylation-resistant mutant of SHARPIN revealed that this mark controls the linear ubiquitination of the NF-κB regulator NEMO and allows the optimal activation of NF-κB in response to TNFα. These results identify an additional layer of regulation of the LUBAC and unveil potential strategies to modulate its action.
Identifiants
pubmed: 33392484
doi: 10.1016/j.isci.2020.101939
pii: S2589-0042(20)31136-6
pmc: PMC7773595
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101939Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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