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Cell Death Differ
2015[May]; 22
(5
): 801-14
PMID25361079
show ga
The Wnt/?-catenin signaling pathway has emerged as a key regulator of complex
biological processes, such as embryonic development, cell proliferation, cell
fate decision and tumorigenesis. Recent studies have shown that the deregulation
of Wnt/?-catenin signaling is frequently observed and leads to abnormal cell
growth in human breast cancer cells. In this study, we identified a novel
regulatory mechanism of Wnt/?-catenin signaling through RARRES3 that targets and
modulates the acylation status of Wnt proteins and co-receptor low-density
lipoprotein receptor-related protein 6, resulting in the suppression of
epithelial-mesenchymal transition and cancer stem cell properties. Mutation of
the conserved active site residues of RARRES3 indicates that RARRES3 serves as an
acyl protein thioesterase that tethers its target proteins and modulates their
acylation status. Furthermore, the functions of p53 in cell proliferation and
Wnt/?-catenin signaling are significantly associated with the induction of
RARRES3. Thus our findings provide a new insight into the molecular link between
p53, protein acylation and Wnt/?-catenin signaling whereby RARRES3 plays a
pivotal role in modulating the acylation status of signaling proteins.
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