Putative GSK-3β Phosphorylation Sites Mediate SOX4 Lysosomal Degradation Open Access

Cheng, Jessica (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/jw827c12q?locale=en
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Abstract

Sex-determining region Y Box (SOX4) is an intronless gene highly upregulated at the mRNA
and protein level in many different cancers including prostate cancer. Recent evidence has linked
SOX4 with β-catenin stability and the promotion of cell proliferation through the Wnt pathway.
As one of the most commonly misregulated signaling pathways in human malignancies, the Wnt
pathway is a perfect target for cancer treatments. In this paper, we mutated three putative GSK-
3β phosphorylation sites on SOX4 and examined the effects of these sites on SOX4 abundance
and degradation. We treated ARCaPE and LNCaP cell lines with proteasome and endosome
inhibitors in an effort to discover the pathway through which SOX4 is degraded. The results
suggest SOX4 is degraded through the lysosomal pathway. Understanding SOX4 degradation
will provide further insight into the Wnt pathway and may lead to a promising new target for
cancer therapeutics.

Table of Contents

INTRODUCTION...1
HYPOTHESIS...7
METHODS...8
RESULTS...12
DISCUSSION...21
FUTURE DIRECTIONS...24
REFERENCES...28

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