Ajuba Phosphorylation by CDK1 Promotes Cell Proliferation and Tumorigenesis.
J Biol Chem
; 291(28): 14761-72, 2016 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-27226586
ABSTRACT
Recent studies identified the adaptor protein Ajuba as a positive regulator of Yes-associated protein (YAP) oncogenic activity through inhibiting large tumor suppressor (Lats1/2) core kinases of the Hippo pathway, a signaling pathway that plays important roles in cancer. In this study, we define a novel mechanism for phospho-regulation of Ajuba in mitosis and its biological significance in cancer. We found that Ajuba is phosphorylated in vitro and in vivo by cyclin-dependent kinase 1 (CDK1) at Ser(119) and Ser(175) during the G2/M phase of the cell cycle. Mitotic phosphorylation of Ajuba controls the expression of multiple cell cycle regulators; however, it does not affect Hippo signaling activity, nor does it induce epithelial-mesenchymal transition. We further showed that mitotic phosphorylation of Ajuba is sufficient to promote cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo Collectively, our discoveries reveal a previously unrecognized mechanism for Ajuba regulation in mitosis and its role in tumorigenesis.
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Bases de dados:
MEDLINE
Assunto principal:
Proteína Quinase CDC2
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Proliferação de Células
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Proteínas com Domínio LIM
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Carcinogênese
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2016
Tipo de documento:
Article