Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.
Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.
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DOC-1R 过表达通过抑制 CDK2 表达和激活来抑制细胞周期 G1/S 转变
DOI：
10.7150/ijbs.5763
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发表时间：
2013
影响因子：
9.2
通讯作者：
Luo Y
中科院分区：
文献类型：
--
作者：
Liu Q;Liu X;Gao J;Shi X;Hu X;Wang S;Luo Y
DOC-1R（在口腔癌-1相关中缺失）是一种新的推定的肿瘤抑制因子。本研究探讨了DOC-1R的抗肿瘤活性及其分子机制。在DOC-1R过表达的HeLa细胞中，使用流式细胞术、BrdU掺入和CDK2激酶检测来评估细胞表型。此外，RT-PCR和Western blot检测这些细胞中潜在的分子变化。通过GST下拉和免疫沉淀- western blot检测DOC-1R与CDK2蛋白的相互作用。数据显示，DOC-1R过表达抑制G1/S相变，抑制DNA复制，抑制CDK2活性。从分子上看，DOC-1R在mRNA和蛋白水平上抑制CDK2的表达，g1期细胞周期蛋白（cyclin D1和E）水平降低，p21、p27和p53蛋白水平升高。同时，DOC-1R与CDK2相关，通过阻断其与cyclin E和a的关联，抑制CDK2的活化。由此可见，DOC-1R的抗肿瘤作用可能是通过抑制CDK2的表达和活化，负调控G1期进展和G1/S转变而介导的。
DOC-1R (deleted in oral cancer-1 related) is a novel putative tumor suppressor. This study investigated DOC-1R antitumor activity and the underlying molecular mechanisms. Cell phenotypes were assessed using flow cytometry, BrdU incorporation and CDK2 kinase assays in DOC-1R overexpressing HeLa cells. In addition, RT-PCR and Western blot assays were used to detect underlying molecular changes in these cells. The interaction between DOC-1R and CDK2 proteins was assayed by GST pull-down and immunoprecipitation-Western blot assays. The data showed that DOC-1R overexpression inhibited G1/S phase transition, DNA replication and suppressed CDK2 activity. Molecularly, DOC-1R inhibited CDK2 expression at the mRNA and protein levels, and there were decreased levels of G1-phase cyclins (cyclin D1 and E) and elevated levels of p21, p27, and p53 proteins. Meanwhile, DOC-1R associated with CDK2 and inhibited CDK2 activation by obstructing its association with cyclin E and A. In conclusion, the antitumor effects of DOC-1R may be mediated by negatively regulating G1 phase progression and G1/S transition through inhibiting CDK2 expression and activation.
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影响因子：
9.2
作者：
Chan JY
通讯作者：
Chan JY
影响因子：
21.3
作者：
Campaner, Stefano;Doni, Mirko;Amati, Bruno
通讯作者：
Amati, Bruno
影响因子：
5.2
作者：
Neganova, Irina;Vilella, Felipe;Lako, Majlinda
通讯作者：
Lako, Majlinda
Chk1-Cdc25A-cyclin A/CDk2 通路参与辛伐他汀诱导多发性骨髓瘤细胞 S 期细胞周期阻滞和凋亡
影响因子：
5
作者：
Tu, Yong-Sheng;Kang, Xiao-Long;Guan, Yong-Yuan
通讯作者：
Guan, Yong-Yuan
DOI：
10.1016/j.bbrc.2012.07.059
发表时间：
2012-08-17
影响因子：
3.1
作者：
Hwang, Chae Young;Lee, Seung-Min;Kwon, Ki-Sun
通讯作者：
Kwon, Ki-Sun