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Figure S1-S7 from FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2–Mediated Phosphorylation of CENP-A
journal contribution
posted on 2023-03-31, 00:41 authored by Mamoru Takada, Weiguo Zhang, Aussie Suzuki, Taruho S. Kuroda, Zhouliang Yu, Hiroyuki Inuzuka, Daming Gao, Lixin Wan, Ming Zhuang, Lianxin Hu, Bo Zhai, Christopher J. Fry, Kerry Bloom, Guohong Li, Gary H. Karpen, Wenyi Wei, Qing ZhangSupplemental Figures for "FBW7 loss promotes chromosomal instability and tumorigenesis via Cyclin E1/CDK2-mediated phosphorylation of CENP-A"
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University Cancer Research Fund
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ARTICLE ABSTRACT
The centromere regulates proper chromosome segregation, and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little is known about how centromere dysfunction occurs in cancer. Here, we define the consequences of phosphorylation by cyclin E1/CDK2 on a conserved Ser18 residue of centromere-associated protein CENP-A, an essential histone H3 variant that specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon loss of FBW7, a tumor suppressor whose inactivation leads to CIN. This event on CENP-A reduced its centromeric localization, increased CIN, and promoted anchorage-independent growth and xenograft tumor formation. Overall, our results revealed a pathway that cyclin E1/CDK2 activation coupled with FBW7 loss promotes CIN and tumor progression via CENP-A–mediated centromere dysfunction. Cancer Res; 77(18); 4881–93. ©2017 AACR.Usage metrics
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BiomarkersCarcinogenesisSignal transductionTumor initiation and promotionCell SignalingDna Damage And RepairGenomic instabilityDrug TargetsOncoprotein & tumor suppressor drug targetsGene RegulationPosttranscriptional and translational controlOncogenes & Tumor SuppressorsTumor suppressor genesProgression, Invasion & MetastasisTumor progression
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