Abstract

Ras family GTPases are critical components of cell regulatory systems that control proliferation, differentiation, and cell survival. Inappropriate regulation of these systems directly contributes to initiation and progression of human cancer. This proposal is directed at increasing our understanding of the composition, organization, and function of cell regulatory networks engaged by Ras family GTPases. Our focus is on the dominant effector pathways that mediate oncogenic Ras-induced cell transformation.
Our specific aims are 1) revealing the molecular basis of the contribution of Ral GTPases to support of human tumor cell proliferation and survival; 2) assessing the role of two candidate Ras effectors in limiting cellular responses to mitogenic signals; and 3) defining the contribution of scaffolding proteins to the generation of signal fidelity on the ERK1/2 MAP kinase cascade..

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA071443-12S1
Application #
7541489
Study Section
Cellular Signaling and Dynamics Study Section (CSD)
Program Officer
Ogunbiyi, Peter
Project Start
1996-08-15
Project End
2010-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
12
Fiscal Year
2008
Total Cost
$59,275
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Cooper, Jonathan M; Ou, Yi-Hung; McMillan, Elizabeth A et al. (2017) TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer. Cancer Res 77:5077-5094
Wang, Chensu; Niederstrasser, Hanspeter; Douglas, Peter M et al. (2017) Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan. Nat Commun 8:2270
Eskiocak, Banu; McMillan, Elizabeth A; Mendiratta, Saurabh et al. (2017) Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma. Cancer Discov 7:832-851
Wang, Chensu; Zhao, Tian; Li, Yang et al. (2017) Investigation of endosome and lysosome biology by ultra pH-sensitive nanoprobes. Adv Drug Deliv Rev 113:87-96
Thomas, Jemima C; Cooper, Jonathan M; Clayton, Natasha S et al. (2016) Inhibition of Ral GTPases Using a Stapled Peptide Approach. J Biol Chem 291:18310-25
Borkowski, Robert; Du, Liqin; Zhao, Zhenze et al. (2015) Genetic mutation of p53 and suppression of the miR-17?92 cluster are synthetic lethal in non-small cell lung cancer due to upregulation of vitamin D Signaling. Cancer Res 75:666-75
Potts, Malia B; McMillan, Elizabeth A; Rosales, Tracy I et al. (2015) Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B. Nat Chem Biol 11:401-8
Torres, Michael J; Pandita, Raj K; Kulak, Ozlem et al. (2015) Role of the Exocyst Complex Component Sec6/8 in Genomic Stability. Mol Cell Biol 35:3633-45
Wang, Chensu; Wang, Yiguang; Li, Yang et al. (2015) A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles. Nat Commun 6:8524
Shields, Benjamin B; Pecot, Chad V; Gao, Hua et al. (2015) A genome-scale screen reveals context-dependent ovarian cancer sensitivity to miRNA overexpression. Mol Syst Biol 11:842

Showing the most recent 10 out of 63 publications