Nuclear β-catenin expression is positively regulated by JAB1 in human colorectal cancer cells
Nuclear β-catenin expression is positively regulated by JAB1 in human colorectal cancer cells
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DOI：
10.1016/j.bbrc.2020.09.007
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发表时间：
2020-12-10
影响因子：
3.1
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Nishimoto, Arata;Takemoto, Yoshihiro;Hamano, Kimikazu
Wnt/β-catenin信号通路在结直肠癌（CRC）的发生发展中起重要作用。β-连环蛋白的降解复合物在CRC细胞中功能受损，从而导致β-连环蛋白的积累及其易位到细胞核中。核β-连环蛋白与T细胞因子4（TCF 4）相互作用并共活化，导致β-连环蛋白/TCF 4依赖性转录。因此，核β-连环蛋白已被归类为CRC肿瘤发生的主要驱动力。最近的研究表明，Jun激活结构域结合蛋白1（JAB 1）增强了7缺席同源物-1（SIAH-1）的降解，SIAH-1是一种推定的β-连环蛋白的E3泛素连接酶，并正调控人CRC细胞中总β-连环蛋白的表达。另一项最近的研究也表明，细胞核β-连环蛋白被泛素化并被E3泛素连接酶降解，三重基序蛋白33（TRIM 33）。然而，核β-连环蛋白表达的调控机制仍有待充分理解。在这项研究中，我们已经证明，JAB 1积极调节细胞核β-连环蛋白，c-MYC作为β-连环蛋白/TCF 4的目标，和细胞周期调节因子，如Ki-67和拓扑异构酶II α在人类CRC细胞的表达。总之，这些结果表明，JAB 1被认为是一个有前途的新的CRC治疗的目标。(C)2020由Elsevier Inc.出版。
Wnt/beta-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for beta-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of beta-catenin and its translocation into the nucleus. Nuclear beta-catenin interacts with and coactivates T cell factor4 (TCF4), resulting in beta-catenin/TCF4-dependent transcription. Therefore, nuclear beta-catenin has been categorized as the main driving force in the tumorigenesis of CRC. Recent studies reveal that Jun activation domain-binding protein 1 (JAB1) enhances the degradation of seven in absentia homolog-1 (SIAH-1), a putative E3 ubiquitin ligase of beta-catenin, and positively regulates the expression of total beta-catenin in human CRC cells. An another recent study also shows that nuclear beta-catenin is ubiquitinated and degraded by an E3 ubiquitin ligase, tripartite motif-containing protein 33 (TRIM33). However, the regulatory mechanism for the expression of nuclear beta-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear beta-catenin, c-MYC as a beta-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase II alpha in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy. (C) 2020 Published by Elsevier Inc.