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. 2015 Feb 25;2(4):e999512.
doi: 10.1080/23723556.2014.999512. eCollection 2015 Oct-Dec.

RARRES3 regulates signal transduction through post-translational protein modifications

Tzu-Hui Hsu  1 , Tsu-Chung Chang  2
Affiliations

RARRES3 regulates signal transduction through post-translational protein modifications

Tzu-Hui Hsu et al. Mol Cell Oncol. .

Abstract

We recently reported that retinoic acid receptor responder 3 (RARRES3)-mediated protein deacylation resulted in significant inhibition of the transformed properties of breast cancer cells. This finding suggests a key role of RARRES3 in the regulation of growth signaling and metastasis in cancer cells and as a potential therapeutic target for cancer therapy.

Keywords: RARRES3; Wnt/β-catenin pathway; protein acylation.

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Figures

Figure 1.
Figure 1.
Role of the p53–RARRES3 axis in the control of Wnt/β-catenin signaling. p53, a type I tumor suppressor, induces the expression of RARRES3, which exerts its tumor suppressive activity through the modulation of Wnt/β-catenin signaling. The increased expression of RARRES3 causes protein deacylation of Wnt/β-catenin signaling molecules, leading to retention of LRP6 in the Golgi apparatus and suppression of Wnt/β-catenin signaling activity. Inhibition of Wnt/β-catenin signaling results in GSK3β-mediated phosphorylation of β-catenin. The subsequent ubiquitination and degradation of β-catenin disrupts β-catenin translocation, leading to suppression of the transformed properties of human cancer cells, including cell proliferation, EMT, and stemness profiles of breast cancer cells. Abbreviations: EMT: epithelial-mesenchymal transition; GSK3β: glycogen synthase kinase 3β; LRP6: lipoprotein receptor-related protein 6; p53RE: p53 response element; RARRES3: retinoic acid receptor responder 3.
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