Putative GSK-3β Phosphorylation Sites Mediate SOX4 Lysosomal Degradation Public
Cheng, Jessica (2011)
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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