Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Dr. Eva Turley

Abstract

Overexpression of a RHAMM isoform (RHAMMΔ163) transforms fibroblasts but the mechanisms underlying this oncogenic function are not well understood. RHAMMΔ163 binds to the mitotic spindle and centrosomes via a C-terminal leucine zipper; these interactions are predicted to regulate genomic stability and cell polarity and proposed to account for the oncogenic function of RHAMMΔ163. We hypothesized that RHAMM leucine zipper maintains mitotic spindle integrity and impacts directional cell migration through its interactions with microtubule and centrosome structures. The consequences of a mutated leucine zipper on cell division, cell motility, and tumorigenesis were assessed. Although mutant RHAMMΔ163 promoted polycentrosomy, it did not alter cell cycle progression and did not strongly affect proliferation or tumorigenesis. However, loss of the leucine zipper function blocked directional movement of fibroblasts without affecting rate of motility. These results suggest that the RHAMM leucine zipper selectively regulates directed migration, which is a centrosome function that contributes to tumorigenesis.

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