Methylation of Aurora kinase A by MMSET reduces p53 stability and regulates cell proliferation and apoptosis.
Oncogene
; 37(48): 6212-6224, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30013191
ABSTRACT
The histone methyltransferase multiple myeloma SET domain protein (MMSET/WHSC1) is highly expressed in diverse tumor types, and its expression appears to be involved in cell proliferation. In this study, we report that MMSET interacts with and methylates Aurora kinase A (AURKA). We show that MMSET-mediated methylation of AURKA induces interaction with p53 as well as enhanced kinase activity of AURKA, which results in the proteasomal degradation of p53. MMSET-mediated p53 degradation increases cell proliferation and results in oncogenic activity. Furthermore, knockdown of MMSET potently inhibits tumorigenic cells and renders them sensitive to growth inhibition by the therapeutic drug, alisertib (AURKA inhibitor). Taken together, our results suggest that MMSET is a regulator of p53 stability via methylation of AURKA in proliferating cells and might be a potential therapeutic target in solid tumors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Proteína Supressora de Tumor p53
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Histona-Lisina N-Metiltransferase
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Apoptose
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Proliferação de Células
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Aurora Quinase A
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article