Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26.
A549 Cells
CRADD Signaling Adaptor Protein
/ genetics
Caspase 2
/ genetics
Cell Differentiation
Centrosome
/ metabolism
Cysteine Endopeptidases
/ genetics
DNA Damage
Death Domain Receptor Signaling Adaptor Proteins
/ genetics
Gene Expression Regulation
HEK293 Cells
Humans
Intercellular Signaling Peptides and Proteins
/ genetics
Signal Transduction
Tumor Suppressor Protein p53
/ genetics
PIDDosome
cell cycle
centrosome
p53
proteolysis
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
received:
03
03
2020
revised:
22
10
2020
accepted:
04
11
2020
pubmed:
23
12
2020
medline:
21
10
2021
entrez:
22
12
2020
Statut:
ppublish
Résumé
Centrosome amplification results into genetic instability and predisposes cells to neoplastic transformation. Supernumerary centrosomes trigger p53 stabilization dependent on the PIDDosome (a multiprotein complex composed by PIDD1, RAIDD and Caspase-2), whose activation results in cleavage of p53's key inhibitor, MDM2. Here, we demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26. PIDDosome-dependent Caspase-2 activation requires not only PIDD1 centrosomal localization, but also its autoproteolysis. Following cytokinesis failure, supernumerary centrosomes form clusters, which appear to be necessary for PIDDosome activation. In addition, in the context of DNA damage, activation of the complex results from a p53-dependent elevation of PIDD1 levels independently of centrosome amplification. We propose that PIDDosome activation can in both cases be promoted by an ANKRD26-dependent local increase in PIDD1 concentration close to the centrosome. Collectively, these findings provide a paradigm for how centrosomes can contribute to cell fate determination by igniting a signalling cascade.
Identifiants
pubmed: 33350486
doi: 10.15252/embj.2020104844
pmc: PMC7883297
doi:
Substances chimiques
ANKRD26 protein, human
0
CRADD Signaling Adaptor Protein
0
CRADD protein, human
0
Death Domain Receptor Signaling Adaptor Proteins
0
Intercellular Signaling Peptides and Proteins
0
PIDD1 protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
CASP2 protein, human
EC 3.4.22.-
Caspase 2
EC 3.4.22.-
Cysteine Endopeptidases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e104844Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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