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New insights into the regulation of Axin function in canonical Wnt signaling pathway 被引量:16

New insights into the regulation of Axin function in canonical Wnt signaling pathway
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摘要 The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling: on one hand, Axin scaffolds the "l^-catenin destruction complex" to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the "on" or "off" Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling. The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling: on one hand, Axin scaffolds the "l^-catenin destruction complex" to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the "on" or "off" Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.
出处 《Protein & Cell》 SCIE CAS CSCD 2014年第3期186-193,共8页 蛋白质与细胞(英文版)
关键词 Wnt signaling AXIN post-transcriptionalmodification POLYMERIZATION auto-inhibition Wnt signaling, Axin, post-transcriptionalmodification, polymerization, auto-inhibition
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