The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.
Alzheimer Disease
/ metabolism
Animals
Cells, Cultured
Chromobox Protein Homolog 5
/ genetics
DNA Transposable Elements
/ genetics
Drosophila
/ metabolism
Drosophila Proteins
/ antagonists & inhibitors
Heterochromatin
/ metabolism
Humans
Lamin Type B
/ chemistry
Mice
Mice, Inbred C57BL
NIMA-Interacting Peptidylprolyl Isomerase
/ antagonists & inhibitors
Neocortex
/ cytology
Neurons
/ cytology
Nuclear Envelope
/ chemistry
Peptidylprolyl Isomerase
/ antagonists & inhibitors
Phosphorylation
RNA Interference
RNA, Small Interfering
/ metabolism
Stress, Mechanical
Drosophila
HP1
Lamin
PIN1
heterochromatin
mechanical stress
neurodegeneration
nuclear envelope
phosphorylation
transposons
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
received:
16
02
2021
revised:
29
06
2021
accepted:
19
08
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
16
2
2022
Statut:
ppublish
Résumé
Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer's disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.
Identifiants
pubmed: 34525372
pii: S2211-1247(21)01141-4
doi: 10.1016/j.celrep.2021.109694
pii:
doi:
Substances chimiques
DNA Transposable Elements
0
Drosophila Proteins
0
Heterochromatin
0
Lamin Type B
0
NIMA-Interacting Peptidylprolyl Isomerase
0
RNA, Small Interfering
0
Chromobox Protein Homolog 5
107283-02-3
Peptidylprolyl Isomerase
EC 5.2.1.8
dod protein, Drosophila
EC 5.2.1.8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109694Subventions
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017216
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.