Nucleosome assembly proteins NAP1L1 and NAP1L4 modulate p53 acetylation to regulate cell fate.
Biochim Biophys Acta Mol Cell Res
; 1866(12): 118560, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31634504
ABSTRACT
The p53 tumor suppressor regulates expression of genes involved in various stress responses. Upon genotoxic stress, p53 induces target genes regulating cell cycle arrest for survival or apoptosis. Nevertheless, detailed mechanisms of how p53 selectively regulates these opposing outcomes remain unclear. For this study, we investigated p53 regulatory mechanisms exerted by nucleosome assembly protein 1-like 1 (NAP1L1) and NAP1L4, both of which are identified as DGKζ-interacting proteins. Here we demonstrate that, under normal conditions, NAP1L1 knockdown decreases Lys320 acetylation of p53 with attenuated proarrest p21 expression, whereas NAP1L4 knockdown increases Lys320 acetylation with enhanced p21 expression. These conditions lead respectively to facilitation and suppression of cell growth. Under genotoxic stress conditions, NAP1L1 knockdown increases Lys382 acetylation with enhanced proapoptotic Bax levels, thereby facilitating cell death. By contrast, NAP1L4 knockdown decreases Lys382 acetylation with attenuated Bax levels, thereby suppressing apoptosis. These results suggest that NAP1L1 and NAP1L4 regulate cell fate by controlling the expression of p53-responsive proarrest and proapoptotic genes through selective modulation of p53 acetylation at specific sites during normal homeostasis and in stress-induced responses.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Nucleossomos
/
Proteína Supressora de Tumor p53
/
Apoptose
/
Proteína 1 de Modelagem do Nucleossomo
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2019
Tipo de documento:
Article