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Int J Biol Sci 2013; 9(6):541-549. doi:10.7150/ijbs.5763

Research Paper

Overexpression of DOC-1R Inhibits Cell Cycle G1/S Transition by Repressing CDK2 Expression and Activation

Qi Liu, Xing Liu, Jinlan Gao, Xiuyan Shi, Xihua Hu, Shusen Wang, Yang Luo

The Research Center for Medical Genomics, MOH Key Laboratory of Cell Biology and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.

Abstract

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.

Keywords: DOC-1R, CDK2, G1/S transition, cyclin E, cyclin A, CKI.

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How to cite this article:
Liu Q, Liu X, Gao J, Shi X, Hu X, Wang S, Luo Y. Overexpression of DOC-1R Inhibits Cell Cycle G1/S Transition by Repressing CDK2 Expression and Activation. Int J Biol Sci 2013; 9(6):541-549. doi:10.7150/ijbs.5763. Available from http://www.ijbs.com/v09p0541.htm