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关键词： 公路桥梁   伸缩缝施工   质量技术  

摘要： 做好道路桥梁,保证桥梁工程的质量,是道路桥梁工作的重要保障,在道路建设中我国逐步增加了道路桥梁建设的数量,对桥梁建设施工的质量要求也愈发严格,公路桥梁建设工作在我国经济发展过程中占有重要地位,保证伸缩缝施工的优良质量,提高施工的技术水平,使桥梁建筑行业在发展中能够越来越好.

关键词： ADENOMATOUS POLYPOSIS-COLI   TUMOR-SUPPRESSOR PROTEIN   SYNTHASE KINASE 3-BETA   WNT SIGNALING PATHWAY   STRUCTURAL BASIS   SUBSTRATE-SPECIFICITY   NEGATIVE REGULATOR   SOMATIC MUTATIONS   CRYSTAL-STRUCTURE   UBIQUITIN LIGASE  

摘要： The Wnt/beta-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by beta-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, initiated by the multi-protein beta-catenin destruction complex. The precise mechanisms underlying destruction complex function have remained unknown, largely because of the lack of suitable in vitro systems. Here we describe the in vitro reconstitution of an active human beta-catenin destruction complex from purified components, recapitulating complex assembly, beta-catenin modification, and degradation. We reveal that AXIN1 polymerization and APC promote beta-catenin capture, phosphorylation, and ubiquitylation. APC facilitates beta-catenin's flux through the complex by limiting ubiquitylation processivity and directly interacts with the SCF beta-TrCP E3 ligase complex in a beta-TrCP-dependent manner. Oncogenic APC truncation variants, although part of the complex, are functionally impaired. Nonetheless, even the most severely truncated APC variant promotes beta-catenin recruitment. These findings exemplify the power of biochemical reconstitution to interrogate the molecular mechanisms of Wnt/beta-catenin signaling.