TY - JOUR
T1 - Ajuba phosphorylation by CDK1 promotes cell proliferation and tumorigenesis
AU - Chen, Xingcheng
AU - Stauffer, Seth
AU - Chen, Yuanhong
AU - Dong, Jixin
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/7/8
Y1 - 2016/7/8
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M116.722751
DO - 10.1074/jbc.M116.722751
M3 - Article
C2 - 27226586
AN - SCOPUS:84978971591
SN - 0021-9258
VL - 291
SP - 14761
EP - 14772
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -