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细胞周期蛋白依赖性激酶1(CDK1)与iASPP相互作用,通过p53途径调节结肠癌细胞增殖。

CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway.

作者信息

Gan Wei, Zhao Hua, Li Tiegang, Liu Kuijie, Huang Jiangsheng

机构信息

Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.

Department of Minimally Invasive Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.

出版信息

Oncotarget. 2017 May 11;8(42):71618-71629. doi: 10.18632/oncotarget.17794. eCollection 2017 Sep 22.

Abstract

CDK1 (cyclin-dependent kinase 1) is a critical regulator of the G2-M checkpoint. CDK1 is considered a possible target for cancer treatment. In addition to CDK1, iASPP plays essential role in maintaining cancer cell proliferation. In the present study, we monitored the expression of CDK1 and iASPP at mRNA and protein levels in CRC tissues and cell lines; we also predicted that iASPP protein might interact with CDK1 protein. By performing GST pull-down assay and Co-IP assay, we confirmed the interaction of CDK1 and iASPP protein. In CRC cell lines, CDK1 interacted with iASPP to affect CRC cell proliferation and apoptosis; moreover, the p53 apoptosis pathway was involved in this progression. Taken together, we revealed that CDK1 and iASPP was up-regulated in CRC tissues and cell lines; CDK1 protein interacted with iASPP protein to affect CRC cell proliferation and apoptosis through the p53 apoptosis pathway. CDK1 and iASPP might serve as not only promising targets in CRC treatment, but also efficient prognostic markers. From the perspective of protein interactions, we provided a novel theoretical basis for targeted therapy of CRC.

摘要

细胞周期蛋白依赖性激酶1(CDK1)是G2-M期检查点的关键调节因子。CDK1被认为是癌症治疗的一个可能靶点。除CDK1外,iASPP在维持癌细胞增殖中起重要作用。在本研究中,我们监测了CDK1和iASPP在结直肠癌组织和细胞系中的mRNA和蛋白质水平表达;我们还预测iASPP蛋白可能与CDK1蛋白相互作用。通过进行谷胱甘肽S-转移酶下拉试验和免疫共沉淀试验,我们证实了CDK1和iASPP蛋白之间的相互作用。在结直肠癌细胞系中,CDK1与iASPP相互作用以影响结直肠癌细胞的增殖和凋亡;此外,p53凋亡途径参与了这一过程。综上所述,我们发现CDK1和iASPP在结直肠癌组织和细胞系中上调;CDK1蛋白与iASPP蛋白相互作用,通过p53凋亡途径影响结直肠癌细胞的增殖和凋亡。CDK1和iASPP不仅可能成为结直肠癌治疗中有前景的靶点,还可能成为有效的预后标志物。从蛋白质相互作用的角度,我们为结直肠癌的靶向治疗提供了新的理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/5641076/37128976c464/oncotarget-08-71618-g001.jpg

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