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Beyond cell adhesion: The role of armadillo proteins in the heart (Review)

机译:超越细胞粘附:犰狳蛋白在心脏中的作用(综述)

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摘要

Plakoglobin (PG, γ-Catenin, JUP), a member of the armadillo protein family and close homolog of β-catenin, functions to link cell surface cadherin molecules with the cytoskeleton. PG is the only junctional component found in both desmosomes and adherens junctions and thus plays a critical role in the regulation of cell-cell adhesion. Similar to β-catenin, PG is able to interact with components of the Wnt signaling pathway and directly affect gene expression by binding with LEF/TCF transcription factors. In addition, it has been proposed that PG functions primarily as a competitive inhibitor of β-catenin transcriptional activity by sequestering LEF/TCF. Compared to β-catenin, the contribution of PG as a transcriptional regulator in either physiological or pathological conditions is poorly understood. There is increasing clinical interest in PG as both a structural protein as well as a signaling molecule as mutations have been identified in the human PG gene that cause Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and cutaneous syndromes. This review will discuss the connection between altered cell adhesion and gene expression and its contribution to disease pathogenesis.
机译:Plagagloglobin(PG,γ-Catenin,JUP)是犰狳蛋白质家族的成员,是β-catenin的紧密同源物,具有将细胞表面钙粘蛋白分子与细胞骨架连接的功能。 PG是在桥粒和粘附连接中发现的唯一连接成分,因此在调节细胞间粘附方面起着至关重要的作用。 PG与β-catenin相似,能够与Wnt信号通路的成分相互作用,并通过与LEF / TCF转录因子结合而直接影响基因表达。另外,已经提出,PG主要通过螯合LEF / TCF而起β-catenin转录活性的竞争性抑制剂的作用。与β-连环蛋白相比,在生理或病理条件下PG作为转录调节因子的贡献知之甚少。由于已经在人PG基因中鉴定出引起心律失常性右心室心肌病(ARVC)和皮肤综合症的突变,因此作为结构蛋白和信号分子的PG在临床上越来越受到关注。这篇综述将讨论改变的细胞粘附和基因表达之间的联系及其对疾病发病机理的贡献。

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