Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Autophagy
/ physiology
Cell Line
Co-Repressor Proteins
Cytoplasm
/ metabolism
Drosophila
Female
Gene Knockdown Techniques
HEK293 Cells
HeLa Cells
Humans
Kelch-Like ECH-Associated Protein 1
/ metabolism
Male
Mice
Molecular Chaperones
NF-E2-Related Factor 2
/ metabolism
Nuclear Proteins
/ genetics
Protein Binding
Protein Folding
Protein Interaction Domains and Motifs
RNA-Binding Proteins
/ metabolism
Sequestosome-1 Protein
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 08 2019
21 08 2019
Historique:
received:
21
06
2018
accepted:
18
07
2019
entrez:
23
8
2019
pubmed:
23
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery for their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical for its function as a cargo receptor. The regulation of p62 phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening and complementary approaches, we found that DAXX physically interacts with p62. Cytoplasmic DAXX promotes p62 puncta formation. We further elucidate that DAXX drives p62 liquid phase condensation by inducing p62 oligomerisation. This effect promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated stress response. The present study suggests a mechanism of p62 phase condensation by a protein interaction, and indicates that DAXX regulates redox homoeostasis, providing a mechanistic insight into the prosurvival function of DAXX.
Identifiants
pubmed: 31434890
doi: 10.1038/s41467-019-11671-2
pii: 10.1038/s41467-019-11671-2
pmc: PMC6704147
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Co-Repressor Proteins
0
DAXX protein, human
0
KEAP1 protein, human
0
Kelch-Like ECH-Associated Protein 1
0
Molecular Chaperones
0
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Nuclear Proteins
0
P62 protein, human
0
RNA-Binding Proteins
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3759Subventions
Organisme : NIAID NIH HHS
ID : R21 AI105794
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L02392X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M023605/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI119069
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA056036
Pays : United States
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