Work

MYC Can Enforce Cell Cycle Transit from G1 to S and G2 to S, But not Mitotic Cellular Division, Independent of p27 Inhibition of Cyclin E/CDK2

Year: 2006

Type: article

Abstract: 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 G1 to S phase; inhibited at lower but not higher levels of MYC transit from G2 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.

Source: Cell Cycle

DOI: 10.4161/cc.5.12.2860

Authors: Debabrita Deb-Basu, Åsa Karlsson, Qing Li, Chi V. Dang, Dean W. Felsher

Institutions: Stanford Medicine, Stanford University, Johns Hopkins University, Johns Hopkins Medicine, Sidney Kimmel Comprehensive Cancer Center

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Damon Runyon Cancer Research Foundation, Leukemia and Lymphoma Society, National Institutes of Health, National Cancer Institute