title: Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.
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.
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Jinlan
authors.initials: J
authors.lastname: Gao
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Shi
authors.forename: Xihua
authors.initials: X
authors.lastname: Hu
authors.forename: Shusen
authors.initials: S
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D016193:G1 Phase; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics*; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D014158:Transcription, Genetic
chemical_list: C401561:CDK2AP2 protein, human; D019925:Cyclin A; D019927:Cyclin E; D015513:Oncogene Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: CDK2; CKI.; DOC-1R; G1/S transition; cyclin A; cyclin E