Causal ALS genes impact the MHC class II antigen presentation pathway.
ALS
C9ORF72
FUS
MHC II
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 09 2023
26 09 2023
Historique:
medline:
20
9
2023
pubmed:
18
9
2023
entrez:
18
9
2023
Statut:
ppublish
Résumé
Mutations in RNA/DNA-binding proteins cause amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain unclear. Here, we report that a set of ALS-associated proteins, namely FUS, EWSR1, TAF15, and MATR3, impact the expression of genes encoding the major histocompatibility complex II (MHC II) antigen presentation pathway. Both subunits of the MHC II heterodimer, HLA-DR, are down-regulated in ALS gene knockouts/knockdown in HeLa and human microglial cells, due to loss of the MHC II transcription factor CIITA. Importantly, hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells bearing the FUS
Identifiants
pubmed: 37722062
doi: 10.1073/pnas.2305756120
pmc: PMC10523463
doi:
Substances chimiques
MATR3 protein, human
0
RNA-Binding Proteins
0
Nuclear Matrix-Associated Proteins
0
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
e2305756120Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM122524
Pays : United States
Commentaires et corrections
Type : CommentIn
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