Publication Date

2018

Document Type

Thesis

Committee Members

Kwang-Jin Cho (Advisor), Daniel Ketcha (Committee Member), Weiwen Long (Committee Member), Michael Markey (Committee Member), Hongmei Ren (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Ras proteins were the first human oncogenes discovered. Although Ras has been found to be the most frequently mutated oncogene, there are currently no anti-Ras-specific drugs available in the clinic. Ras is responsible for initiating cellular pathways that include proliferation, survival, and apoptosis. There are three ubiquitously expressed Ras isoforms in mammalian cells: H-, N-, and K-Ras. Interaction with the plasma membrane is required for Ras biological activity. When Ras interaction with the plasma membrane is blocked, Ras activity is inhibited. Two compounds (from Dr. Ketcha, WSU Chemistry Department) were tested and shown to dissociate K-Ras, but not H-Ras from the plasma membrane. The molecular mechanism was found to be through phosphorylation of K-Ras Ser181. Furthermore, these compounds block signal output of K-Ras, but not H-Ras, and inhibit the growth of K-Ras-driven non-small cell lung cancer cells. Further characterization of these compounds could lead to the development of anti-K-Ras drugs.

Page Count

72

Department or Program

Department of Biochemistry and Molecular Biology

Year Degree Awarded

2018

ORCID ID

0000-0002-5268-6038


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