The role of acetylation sites in the regulation of p53 activity.
Mol Biol Rep
; 47(1): 381-391, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31680191
ABSTRACT
As a "genomic guardian", p53 mainly functions as a transcription factor that regulates downstream targets responsible for cell fate control, and the activity of p53 is tightly regulated by a complex network that include an abundance of post-translational modifications. Notably, acetylation of p53 at many positions has been demonstrated to play a major role in accurate p53 regulation and cell fate determination. However, no evidence has been provided to compare the effect of acetylation at different sites on p53 regulation. Here, we constructed six acetylation-defective p53 mutants that lysine was substituted by arginine at residues 120, 164, 305, 320, 370/372/373 or 381/382/386, respectively, and determined their effects on p53 activity systematically. Our results showed that all six mutants exhibited diminished transactivation ability and selective regulation of target genes expression through distinct mechanisms. Specifically, lysine 370/372/373 and 381/382/386 mutations decreased p53 stability, and lysine 305 mutation reduced p53 phosphorylation level at serine 15, while lysine 120 and 164 mutations decreased p53 acetylation level at lysine 382. Collectively, these data indicate that acetylation of p53 at different sites has diverse regulatory effects on p53 transcriptional activity through different mechanisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Proteína Supressora de Tumor p53
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China