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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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References

    1. DiSepio D, Ghosn C, Eckert RL, Deucher A, Robinson N, Duvic M, Chandraratna RA. Nagpal S. Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene. Proc Natl Acad Sci USA 1998; 95:14811-14815; PMID:9843971; http://dx.doi.org/ 10.1073/pnas.95.25.14811 - DOI - PMC - PubMed
    1. Anantharaman V, Aravind L. Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes. Genome Biol 2003; 4:R11; http://dx.doi.org/ 10.1186/gb-2003-4-2-r11 - DOI - PMC - PubMed
    1. Hsu TH, Chu CC, Jiang SY, Hung MW, Ni WC, Lin HE, Chang TC. Expression of the class II tumor suppressor gene RIG1 is directly regulated by p53 tumor suppressor in cancer cell lines. FEBS Lett 2012; 586:1287-1293; http://dx.doi.org/ 10.1016/j.febslet.2012.03.020 - DOI - PubMed
    1. Hsu TH, Jiang SY, Chan WL, Eckert RL, Scharadin TM, Chang T-C. Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells. Cell Death Differ, 2015; 22:801-814; http://dx.doi.org/ 10.1038/cdd.2014.175. - DOI - PMC - PubMed
    1. Morales M, Arenas EJ, Urosevic J, Guiu M, Fernandez E, Planet E, Fenwick RB, Fernandez-Ruiz S, Salvatella X, Reverter D, Carracedo A, Massague J, Gomis RR. RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation. EMBO Mol Med 2014; 6:865-881; http://dx.doi.org/ 10.15252/emmm.201303675 - DOI - PMC - PubMed

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