A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA.
Amino Acid Sequence
Cytosol
/ metabolism
DNA
/ metabolism
Fatty Acids, Unsaturated
/ pharmacology
HEK293 Cells
HeLa Cells
Humans
Immunity, Innate
Interferon Type I
/ drug effects
Interferon-beta
/ metabolism
Karyopherins
/ drug effects
Membrane Proteins
/ metabolism
Mutation
Nuclear Export Signals
Nucleotides, Cyclic
/ metabolism
Nucleotidyltransferases
/ genetics
Receptors, Cytoplasmic and Nuclear
/ drug effects
Signal Transduction
THP-1 Cells
Exportin 1 Protein
DNA sensor
cGAS
innate immune system
nuclear export signal
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 01 2021
05 01 2021
Historique:
received:
31
10
2019
revised:
02
03
2020
accepted:
10
12
2020
entrez:
6
1
2021
pubmed:
7
1
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
The cyclic GMP-AMP (cGAMP) synthase (cGAS) is a key DNA sensor that initiates STING-dependent signaling to produce type I interferons through synthesizing the secondary messenger 2'3'-cGAMP. In this study, we confirm previous studies showing that cGAS is located both in the cytoplasm and in the nucleus. Nuclear accumulation is observed when leptomycin B is used to block the exportin, CRM1 protein. As a result, leptomycin B impairs the production of interferons in response to DNA stimulation. We further identify a functional nuclear export signal (NES) in cGAS,
Identifiants
pubmed: 33406424
pii: S2211-1247(20)31575-8
doi: 10.1016/j.celrep.2020.108586
pii:
doi:
Substances chimiques
Fatty Acids, Unsaturated
0
Interferon Type I
0
Karyopherins
0
Membrane Proteins
0
Nuclear Export Signals
0
Nucleotides, Cyclic
0
Receptors, Cytoplasmic and Nuclear
0
STING1 protein, human
0
cyclic guanosine monophosphate-adenosine monophosphate
0
Interferon-beta
77238-31-4
DNA
9007-49-2
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
leptomycin B
Y031I2N1EO
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108586Subventions
Organisme : CIHR
ID : CCI-132561
Pays : Canada
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.