An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress.
HSF1
JMJD6
proteostasis
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:
16 Jul 2024
16 Jul 2024
Historique:
medline:
10
7
2024
pubmed:
10
7
2024
entrez:
10
7
2024
Statut:
ppublish
Résumé
Heat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified Jumonji domain-containing protein 6 (JMJD6) as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a noncanonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis. In a positive feedback circuit, HSF1 binds and promotes JMJD6 expression, which in turn reduces heat shock protein 70 (HSP70) R469 monomethylation to disrupt HSP70-HSF1 repressive complexes resulting in enhanced HSF1 activation. Thus, JMJD6 is intricately wired into the proteostasis network where it plays a critical role in cellular adaptation to proteotoxic stress.
Identifiants
pubmed: 38985769
doi: 10.1073/pnas.2313370121
doi:
Substances chimiques
Heat Shock Transcription Factors
0
HSF1 protein, human
0
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
HSP70 Heat-Shock Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2313370121Subventions
Organisme : Foundation for the National Institutes of Health (FNIH)
ID : F30CA264513
Organisme : NIGMS NIH HHS
ID : R01 GM144617
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA070085
Pays : United States
Organisme : HHS | NIH | National Cancer Institute (NCI)
ID : R50CA221848
Organisme : Foundation for the National Institutes of Health (FNIH)
ID : 1R01GM144617-01
Déclaration de conflit d'intérêts
Competing interests statement:The authors declare no competing interest.