The Drosophila Model of Cancer:
Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis
Open Access
Author:
Shimizu, Takeshi
Graduate Program:
Biochemistry, Microbiology, and Molecular Biology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 09, 2006
Committee Members:
Zhi Chun Lai, Committee Chair/Co-Chair Carol V Gay, Committee Member Richard W Ordway, Committee Member Robert Paulson, Committee Member Wendy Hanna Rose, Committee Member
Keywords:
cancer biology tumor suppressor wts lats hpo mats Drosophila
Abstract:
Within this dissertation, I present the discovery and characterization of Drosophila mob as tumour suppressor, mats. It is a gene designated CG13852 by the Berkley Drosophila Genome Project, which encodes a homologue of Saccharomyces cerevisiae mob1. Loss-of-function analyses indicated that mats is involved in the control of cell proliferation, apoptosis, and differentiation. Somatic homozygous mutant clones of mats produce large tumour due to failure in all these processes. mats shows genetic interaction with components of Wts/Lats signalling such that it can increase the growth suppression effects of wts and hpo. mats acts downstream of hpo, but it appears to have both upstream and downstream functions to wts. The function of mats is important for early embryonic development, and it is required for proper DNA segregation. Mats is accumulated at the centrosome with its kinase partner Wts throughout the cell cycle. Mats can be localized both in the nucleus and cytosol, but upon high activity of Wts in the cytosol, it is depleted from the nucleus thereby it elevates growth suppression effect of Wts. mats belongs to the structurally and functionally highly conserved Mob gene family, thus homologues in human may act as tumour suppressive factors.