p38 MAPK inhibits nonsense-mediated RNA decay in response to persistent DNA damage in noncycling cells.
J Biol Chem
; 292(37): 15266-15276, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28765281
ABSTRACT
Persistent DNA damage induces profound alterations in gene expression that, in turn, influence tissue homeostasis, tumorigenesis, and cancer treatment outcome. However, the underlying mechanism for gene expression reprogramming induced by persistent DNA damage remains poorly understood. Here, using a highly effective bioluminescence-based reporter system and other tools, we report that persistent DNA damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, in noncycling cells. NMD suppression by persistent DNA damage required the activity of the p38α MAPK. Activating transcription factor 3 (ATF3), an NMD target and a key stress-inducible transcription factor, was stabilized in a p38α- and NMD-dependent manner following persistent DNA damage. Our results reveal a novel p38α-dependent pathway that regulates NMD activity in response to persistent DNA damage, which, in turn, controls ATF3 expression in affected cells.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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RNA Mensageiro
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Regulação da Expressão Gênica
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Proteína Quinase 14 Ativada por Mitógeno
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Fator 3 Ativador da Transcrição
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Degradação do RNAm Mediada por Códon sem Sentido
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article