DDIT4 gene expression is switched on by a new HDAC4 function in ataxia telangiectasia.
Ataxia Telangiectasia
/ drug therapy
Cell Line
Dexamethasone
/ pharmacology
Gene Expression
/ drug effects
Gene Expression Regulation
/ drug effects
Glucocorticoids
/ pharmacology
Histone Deacetylases
/ genetics
Humans
Neurodegenerative Diseases
/ drug therapy
Repressor Proteins
/ genetics
Signal Transduction
/ drug effects
Transcription Factors
/ genetics
Transcriptional Activation
/ drug effects
Up-Regulation
/ drug effects
DDIT4
HDAC4
ataxia telangiectasia
dexamethasone
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
13
08
2019
revised:
12
10
2019
accepted:
06
11
2019
entrez:
10
1
2020
pubmed:
10
1
2020
medline:
7
7
2020
Statut:
ppublish
Résumé
Ataxia telangiectasia (AT) is a rare, severe, and ineluctably progressive multisystemic neurodegenerative disease. Histone deacetylase 4 (HDAC4) nuclear accumulation has been related to neurodegeneration in AT. Since treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome, the effects of dexamethasone on HDAC4 were investigated. In this paper, we describe a novel nonepigenetic function of HDAC4 induced by dexamethasone, through which it can directly modulate HIF-1a activity and promote the upregulation of the DDIT4 gene and protein expression. This new HDAC4 transcription regulation mechanism leads to a positive effect on autophagic flux, an AT-compromised biological pathway. This signaling was specifically induced by dexamethasone only in AT cell lines and can contribute in explaining the positive effects of dexamethasone observed in AT-treated patients.
Identifiants
pubmed: 31914654
doi: 10.1096/fj.201902039R
doi:
Substances chimiques
DDIT4 protein, human
0
Glucocorticoids
0
Repressor Proteins
0
Transcription Factors
0
Dexamethasone
7S5I7G3JQL
HDAC4 protein, human
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1802-1818Informations de copyright
© 2019 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.
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