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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2013 > Volume 9 Number 6 > Qi Liu, Xing Liu, Jinlan Gao, Xiuyan Shi, Xihua Hu, Shusen Wang, Yang Luo✉

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.

Date Deposited : 11 Apr 2015 09:59

Last Modified : 11 Apr 2015 09:59

Official URL: http://www.ijbs.com/ms/archive

Volume 9, Number 6, - 2013 , ISSN 1449-2288

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