Advisory Committee Chair
Fang-Tsyr Lin
Advisory Committee Members
Susan L Bellis
Etty N Benveniste
Danny R Welch
Document Type
Dissertation
Date of Award
2012
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
TRIP6 is a focal adhesion molecule that functions as an adaptor protein to mediate diverse cellular functions, including motility and antiapoptotic signaling, through a wide variety of protein-protein interactions. We were able to characterize a novel interaction between TRIP6 and p27KIP1, a CDK inhibitor which can both suppress and promote tumorigenesis, depending on its regulation. TRIP6 expression specifically promotes the AKT-mediated phosphorylation of p27KIP1 at T157, which leads to its cytosolic retention, and accelerates the protein turnover rate of p27KIP1. We also found that phosphorylation of T157 by itself promotes cell motility and can be linked to the formation of motility-associated cytoskeletal structures, including podosome-like actin bundles. Finally, we were able to demonstrate that TRIP6 knockdown inhibits tumorigenesis of both ovarian cancer and glioblastoma xenografts in vivo and that its overexpression correlates to poor outcome in human gliomas. Because of these findings, TRIP6 may be useful as a novel prognostic biomarker for the assessment of all human gliomas, as well as a target for future therapeutic interventions.
Recommended Citation
Lin, Victor T G, "Regulation of p27KIP1 by TRIP6 and its implications in cancer progression" (2012). All ETDs from UAB. 2294.
https://digitalcommons.library.uab.edu/etd-collection/2294