Abstract

The goal of the research is to characterize the biological activity of functional mutants of the human rasH oncogene, and to identify the biochemical properties of the rasH protein important for neoplastic transformation. Recently developed structural and functional mutants of normal and activated rasH genes will be introduced into a variety of cell types. Included among these mutants are rasH proteins that are deficient in the binding or hydrolysis of guanine nucleotides. Using mutants of the activated rasH gene, the structural and biochemical properties of the rasH protein which are required for the transformation and tumorigenicity of fibroblasts and epithelial cells will be compared. In vitro cell systems will be established to assay the effects of rasH expression on cellular differentiation, and the rasH protein domains which function in differentiation will be characterized. Finally, in vitro random mutagenesis will be used to generate additional rasH mutants active in the transformation of epithelial cells, and in altering cellular differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA042978-01
Application #
3184782
Study Section
Pathology B Study Section (PTHB)
Project Start
1986-07-01
Project End
1989-12-30
Budget Start
1986-07-01
Budget End
1987-12-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Waters, Andrew M; Der, Channing J (2018) KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer. Cold Spring Harb Perspect Med 8:
Vaseva, Angelina V; Blake, Devon R; Gilbert, Thomas S K et al. (2018) KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism. Cancer Cell 34:807-822.e7
Papke, Bjoern; Der, Channing J (2017) Drugging RAS: Know the enemy. Science 355:1158-1163
Waters, Andrew M; Ozkan-Dagliyan, Irem; Vaseva, Angelina V et al. (2017) Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies. Sci Signal 10:
Yin, Guowei; Kistler, Samantha; George, Samuel D et al. (2017) A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation. J Biol Chem 292:4446-4456
Justilien, Verline; Ali, Syed A; Jamieson, Lee et al. (2017) Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. Cancer Cell 31:256-269
Lawson, Campbell D; Fan, Cheng; Mitin, Natalia et al. (2016) Rho GTPase Transcriptome Analysis Reveals Oncogenic Roles for Rho GTPase-Activating Proteins in Basal-like Breast Cancers. Cancer Res 76:3826-37
Gentry, Leanna R; Karginov, Andrei V; Hahn, Klaus M et al. (2016) Characterization of an Engineered Src Kinase to Study Src Signaling and Biology. Methods Mol Biol 1360:157-67
Zhou, Bingying; Ritt, Daniel A; Morrison, Deborah K et al. (2016) Protein Kinase CK2? Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2? Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma. J Biol Chem 291:17804-15
Hobbs, G Aaron; Der, Channing J; Rossman, Kent L (2016) RAS isoforms and mutations in cancer at a glance. J Cell Sci 129:1287-92

Showing the most recent 10 out of 169 publications