title: Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells.
abstract: The Wnt/β-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/β-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/β-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/β-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/β-catenin signaling whereby RARRES3 plays a pivotal role in modulating the acylation status of signaling proteins.
authors.affiliation: 1] Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC [2] Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: T-H
authors.initials: TH
authors.lastname: Hsu
authors.affiliation: Department of Medical Education and Research, The Buddhist Tzu Chi General Hospital, Taipei, Taiwan, ROC.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Jiang
authors.forename: W-L
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: W-L
authors.initials: WL
authors.lastname: Chan
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA [2] Department of Dermatology, School of Medicine, University of Maryland, Baltimore, MD, USA [3] Department of Obstetrics and Gynecology and Reproductive Sciences, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Eckert
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Scharadin
authors.affiliation: 1] Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC [2] Department of Biotechnology, Asia University, Taichung, Taiwan, ROC [3] Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC [4] Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: T-C
authors.initials: TC
authors.lastname: Chang
mesh_terms: D000215:Acylation; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53