Cyclin E and Cks proteins are frequently overexpressed in a broad spectrum of human cancers, and as we have shown for breast cancer, often in the same tumors. Yet, how these proteins contribute to oncogenesis is poorly understood. Compounding the problem of understanding their roles in oncogenesis is an incomplete delineation of their basic biological functions. In this proposal we aim to address both of these issues. We will use a combination of biochemical, cell based and animal based approaches in the hope of providing a comprehensive picture of how these proteins function individually and in concert during the cell cycle and in oncogenesis.

Public Health Relevance

Cancer is a disease with tremendous health implications for the US and world, and yet, only limited progress has been made in curing most types of cancer. In part, this is because many mechanistic questions concerning the basic biology of cancer remain unanswered. This proposal seeks to address some of these unanswered questions.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Hildesheim, Jeffrey
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Scripps Research Institute
La Jolla
United States
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del Rincón, S V; Widschwendter, M; Sun, D et al. (2015) Cks overexpression enhances chemotherapeutic efficacy by overriding DNA damage checkpoints. Oncogene 34:1961-7
Bhaskaran, Nimesh; van Drogen, Frank; Ng, Hwee-Fang et al. (2013) Fbw7? and Fbw7? collaborate to shuttle cyclin E1 into the nucleolus for multiubiquitylation. Mol Cell Biol 33:85-97
Chuang, Li-Chiou; Teixeira, Leonardo K; Wohlschlegel, James A et al. (2009) Phosphorylation of Mcm2 by Cdc7 promotes pre-replication complex assembly during cell-cycle re-entry. Mol Cell 35:206-16
Best, D Hunter; Coleman, William B (2007) Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. J Hepatol 46:1055-63
Best, D Hunter; Coleman, William B (2007) Bile duct destruction by 4,4'-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. Hepatology 46:1611-9
Rivenbark, Ashley G; Coleman, William B (2007) Dissecting the molecular mechanisms of cancer through bioinformatics-based experimental approaches. J Cell Biochem 101:1074-86
Coleman, William B; Rivenbark, Ashley G (2006) Quantitative DNA methylation analysis: the promise of high-throughput epigenomic diagnostic testing in human neoplastic disease. J Mol Diagn 8:152-6
Spruck, Charles; Sun, Dahui; Fiegl, Heidi et al. (2006) Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. Cancer Res 66:7355-60
Rivenbark, Ashley G; Jones, Wendell D; Risher, J Devon et al. (2006) DNA methylation-dependent epigenetic regulation of gene expression in MCF-7 breast cancer cells. Epigenetics 1:32-44
Smith, A P L; Henze, M; Lee, J A et al. (2006) Deregulated cyclin E promotes p53 loss of heterozygosity and tumorigenesis in the mouse mammary gland. Oncogene 25:7245-59

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