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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Biol+Chem 2016 ; 291 (28): 14761-72 Nephropedia Template TP
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Ajuba Phosphorylation by CDK1 Promotes Cell Proliferation and Tumorigenesis* #MMPMID27226586
Chen X; Stauffer S; Chen Y; Dong J
J Biol Chem 2016[Jul]; 291 (28): 14761-72 PMID27226586show ga
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 Ser119 and Ser175 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.