FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates.
Autophagy
/ genetics
Autophagy-Related Protein-1 Homolog
/ genetics
Autophagy-Related Proteins
/ genetics
Humans
Immunity, Innate
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Neoplasm Proteins
/ genetics
Neurodegenerative Diseases
/ genetics
Phosphorylation
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Sequestosome-1 Protein
/ genetics
Signal Transduction
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 07 2021
05 07 2021
Historique:
received:
10
12
2020
accepted:
07
06
2021
entrez:
6
7
2021
pubmed:
7
7
2021
medline:
5
11
2021
Statut:
epublish
Résumé
The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, and ablation of either function has been linked to neuroinflammatory or degenerative diseases. Autophagy is an intracellular process that recycles old or damaged proteins and organelles. In recent years, the TBK1-dependent regulation of autophagy pathways has been characterized. However, the autophagy-dependent regulation of TBK1 activity awaits further clarification. Here, we observed that TBK1 is recruited to SQSTM1/p62-containing aggregates via the selective autophagy receptor TAX1BP1. In these aggregates, TBK1 phosphorylates SQSTM1/p62 at serine 403 and thus presumably regulates the efficient engulfment and clearance of these structures. We found that TBK1 activation is strongly increased if FIP200, a component of the autophagy-inducing ULK1 complex, is not present or cannot bind to TAX1BP1. Given our collective findings, we hypothesize that FIP200 ensures the inducible activation of TBK1 at SQSTM1/p62 condensates.
Identifiants
pubmed: 34226595
doi: 10.1038/s41598-021-92408-4
pii: 10.1038/s41598-021-92408-4
pmc: PMC8257712
doi:
Substances chimiques
Autophagy-Related Proteins
0
Intracellular Signaling Peptides and Proteins
0
Neoplasm Proteins
0
RB1CC1 protein, human
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
TAX1BP1 protein, human
0
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
TBK1 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13863Références
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