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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA078343-16A1
Application #
8787895
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hildesheim, Jeffrey
Project Start
1998-08-01
Project End
2019-05-31
Budget Start
2014-07-25
Budget End
2015-05-31
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Tat, John; Loriot, Céline; Henze, Martha et al. (2017) CKS protein overexpression renders tumors susceptible to a chemotherapeutic strategy that protects normal tissues. Oncotarget 8:114911-114923
Mu, Ruiling; Tat, John; Zamudio, Robert et al. (2017) CKS Proteins Promote Checkpoint Recovery by Stimulating Phosphorylation of Treslin. Mol Cell Biol 37:
Teixeira, Leonardo K; Reed, Steven I (2016) Cdc6: Skin in the carcinogenesis game. Cell Cycle 15:313
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
Teixeira, Leonardo K; Wang, Xianlong; Li, Yongjiang et al. (2015) Cyclin E deregulation promotes loss of specific genomic regions. Curr Biol 25:1327-33
Sandhu, Rupninder; Rivenbark, Ashley G; Mackler, Randi M et al. (2014) Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer. Int J Oncol 44:563-72
Ekholm-Reed, Susanna; Goldberg, Matthew S; Schlossmacher, Michael G et al. (2013) Parkin-dependent degradation of the F-box protein Fbw7? promotes neuronal survival in response to oxidative stress by stabilizing Mcl-1. Mol Cell Biol 33:3627-43
Teixeira, Leonardo K; Reed, Steven I (2013) Ubiquitin ligases and cell cycle control. Annu Rev Biochem 82:387-414
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
Best, D Hunter; Coleman, William B (2010) Liver regeneration by small hepatocyte-like progenitor cells after necrotic injury by carbon tetrachloride in retrorsine-exposed rats. Exp Mol Pathol 89:92-8

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