کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10142949 | 1646123 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cyclin-dependent kinase 1-mediated phosphorylation of YES links mitotic arrest and apoptosis during antitubulin chemotherapy
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کلمات کلیدی
CRISPRSFKCDK1PLK1Mitotic phosphorylationYAP - ایجادYES - بلهChemotherapy - شیمیدرمانیcyclin-dependent kinase inhibitor 1A - مهار کننده 1A کیناز وابسته به کینازknockout - ناکاوتyes-associated protein - پروتئین مرتبط با بلهPolo-like kinase 1 - پلی کیناز 1Cyclin-dependent kinase 1 - کیناز وابسته به سیکلین 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
YES is a member of the SRC family kinase (SFK) group of non-receptor tyrosine kinases, which are implicated in multiple key cellular processes involved in oncogenesis. Antitubulin agents have been widely used as chemotherapeutics for cancer patients and these drugs arrest cells in mitosis, leading to subsequent cell death. In the present study, we define a mechanism for phospho-regulation of YES that is critical for its role in response to antitubulin agents. Specifically, we found that YES is phosphorylated at multiple sites on its N-terminal unique domain by the cell cycle kinase CDK1 during antitubulin drug-induced mitotic arrest. Phosphorylation of YES occurs during normal mitosis. Deletion of YES causes arrest in prometaphase and polyploidy in a p53-independent manner. We further show that YES regulates antitubulin chemosensitivity. Importantly, mitotic phosphorylation is essential for these effects. In support of our findings, we found that YES expression is high in recurrent ovarian cancer patients. Finally, through expression profiling, we documented that YES phosphorylation affects expression of multiple cell cycle regulators. Collectively, our results reveal a previously unrecognized mechanism for controlling the activity of YES during antitubulin chemotherapeutic treatment and suggest YES as a potential target for the treatment of antitubulin-resistant cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 52, December 2018, Pages 137-146
Journal: Cellular Signalling - Volume 52, December 2018, Pages 137-146
نویسندگان
Zhan Wang, Xingcheng Chen, Mei-Zuo Zhong, Shuping Yang, Jiuli Zhou, David L. Klinkebiel, Adam R. Karpf, Yuanhong Chen, Jixin Dong,