期刊
CELL CYCLE
卷 5, 期 12, 页码 1348-1355出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.5.12.2860
关键词
MYC; p27; CyclinE; CDK2; endo-reduplication
类别
资金
- NCI NIH HHS [3R01 CA89305-0351, T32 CA009151, T32 CA09151, 1R01 CA89305-01A1, 5R37CA051497, 1R01 CA105102, 5T32 CA09302-27] Funding Source: Medline
Overexpression of the MYC proto-oncogene exerts protean biological effects that may contribute to its ability to induce tumorigenesis including enforcing cellular growth and proliferation and inducing genomic instability. MYC overexpression may induce genomic damage at least in part by causing inappropriate DNA replication. MYC may induce inappropriate DNA replication through the activation of Cyclin E/CDK2. To address this possibility, the effects of ectopic p27 expression in immortal rat fibroblasts or human breast epithelial cell lines on MYC-induced endo-reduplication was determined. p27 inhibited Cyclin E/CDK2 associated kinase activity, but failed to prevent MYC from inducing transit from G(1) to S phase; inhibited at lower but not higher levels of MYC transit from G(2) to S and endo-reduplication; however, MYC failed to enforce mitotic cellular division. In addition, MYC was found to induce Cyclin E; and Cyclin E in turn was found to be able to induce endo-reduplication. Hence, MYC appears induce inappropriate cell cycle transit, but not mitotic cellular division independent of p27 mediated inhibition of Cyclin E/Cdk2. Our results have implications for the mechanisms by which MYC overexpression dysregulates cell cycle transit, causes genomic destabilization and is restrained from causing tumorigenesis.
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