The multifaceted allosteric regulation of Aurora kinase A.
Biochem J
; 475(12): 2025-2042, 2018 06 26.
Article
em En
| MEDLINE
| ID: mdl-29946042
ABSTRACT
The protein kinase Aurora A (AurA) is essential for the formation of bipolar mitotic spindles in all eukaryotic organisms. During spindle assembly, AurA is activated through two different pathways operating at centrosomes and on spindle microtubules. Recent studies have revealed that these pathways operate quite differently at the molecular level, activating AurA through multifaceted changes to the structure and dynamics of the kinase domain. These advances provide an intimate atomic-level view of the finely tuned regulatory control operating in protein kinases, revealing mechanisms of allosteric cooperativity that provide graded levels of regulatory control, and a previously unanticipated mechanism for kinase activation by phosphorylation on the activation loop. Here, I review these advances in our understanding of AurA function, and discuss their implications for the use of allosteric small molecule inhibitors to address recently discovered roles of AurA in neuroblastoma, prostate cancer and melanoma.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Aurora Quinase A
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Melanoma
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Proteínas de Neoplasias
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Neuroblastoma
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos