细胞周期蛋白依赖激酶6
基因敲除
癌症研究
泛素
细胞周期蛋白D1
细胞生长
细胞周期
细胞周期检查点
生物
激酶
细胞周期蛋白依赖激酶2
化学
癌症
细胞生物学
蛋白激酶A
细胞培养
基因
遗传学
作者
Kaishu Li,Guanglong Huang,Ziyu Wang,Runwei Yang,Wanghao Zhang,Bowen Ni,Jingyu Guan,Guozhong Yi,Zhiyong Li,Qihui Zhu,Qian Peng,Lunhao Yang,Ling Qi,Yawei Liu
标识
DOI:10.1016/j.bbadis.2022.166571
摘要
Sustained proliferative signaling is a crucial hallmark and therapeutic target in glioblastoma (GBM); however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. In this study, I kappa B kinase interacting protein (IKBIP) was identified to be correlated with the progression of GBM by analysis of The Cancer Genome Atlas (TCGA) data. TCGA database analysis indicated that higher IKBIP expression was associated with high tumor grade and poor prognosis in GBM patients, and these correlations were subsequently validated in clinical samples. IKBIP knockdown induced G1/S arrest by blocking the Cyclin D1/CDK4/CDK6/CDK2 pathway. Our results showed that IKBIP may bind directly to CDK4, a key cell cycle checkpoint protein, and prevent its ubiquitination-mediated degradation in GBM cells. An in vivo study confirmed that IKBIP knockdown strongly suppressed cell proliferation and tumor growth and prolonged survival in a mouse xenograft model established with human GBM cells. In conclusion, IKBIP functions as a novel driver of GBM by binding and stabilizing the CDK4 protein. IKBIP could be a potential therapeutic target in GBM.
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