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哺乳动物Scribble在连接部位的募集依赖于E-钙黏蛋白的结合。

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement.

作者信息

Navarro Christel, Nola Sébastien, Audebert Stéphane, Santoni Marie-Josée, Arsanto Jean-Pierre, Ginestier Christophe, Marchetto Sylvie, Jacquemier Jocelyne, Isnardon Daniel, Le Bivic André, Birnbaum Daniel, Borg Jean-Paul

机构信息

Marseille Cancer Institute, Molecular Pharmacology, UMR 599 Inserm-Institut Paoli-Calmettes, 27 boulevard Leï Roure 13009 Marseille, France.

出版信息

Oncogene. 2005 Jun 23;24(27):4330-9. doi: 10.1038/sj.onc.1208632.

Abstract

Members of the LAP protein family, LET-413 in Caenorhabditis elegans, Scribble in Drosophila melanogaster, and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene. We show here that, in epithelial cells, hScrib is recruited at cell-cell junctions in an E-cadherin-dependent manner as shown by calcium switch assays in MDCK cells, re-expression of E-cadherin in MDA-231 cells treated by 5-Aza-2'-deoxycytidine (5Aza), and siRNA experiments. hScrib is restricted at the basolateral membrane of epithelial cells by its LRR domain, and is enriched in Triton X-100-insoluble fractions. In breast cancers, most lobular tumors did not express hScrib and E-cadherin while ductal tumors had a less frequent downregulation of hScrib. Our data provide additional insights on the modalities of recruitment of hScrib at the cell-cell junctions, and establish a potential link between the E-cadherin and hScrib tumor suppressors.

摘要

LAP蛋白家族成员,秀丽隐杆线虫中的LET-413、黑腹果蝇中的Scribble,以及哺乳动物中的Erbin、Lano、Densin-180和hScrib,具有保守的结构特征。LET-413和Scribble是参与建立和维持上皮细胞极性的连接蛋白。Scribble还表现为一种肿瘤抑制基因。我们在此表明,在上皮细胞中,hScrib以E-钙黏着蛋白依赖的方式被招募到细胞间连接处,这通过MDCK细胞中的钙转换实验、经5-氮杂-2'-脱氧胞苷(5Aza)处理的MDA-231细胞中E-钙黏着蛋白的重新表达以及小干扰RNA实验得以证明。hScrib通过其富含亮氨酸重复序列(LRR)结构域被限制在上皮细胞的基底外侧膜,并在Triton X-100不溶性组分中富集。在乳腺癌中,大多数小叶肿瘤不表达hScrib和E-钙黏着蛋白,而导管肿瘤中hScrib下调的频率较低。我们的数据为hScrib在细胞间连接处的招募方式提供了更多见解,并建立了E-钙黏着蛋白和hScrib肿瘤抑制因子之间的潜在联系。

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