BAG3通过其WW结构域调节胶质母细胞瘤的纤毛稳态。

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-04-24 DOI:10.1002/biof.2060
Caterina Roth, Lara Paulini, Marina E. Hoffmann, Thorsten Mosler, I. Dikič, Andreas Brunschweiger, Hagen Körschgen, Christian Behl, B. Linder, D. Kögel
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引用次数: 0

摘要

多域蛋白 BAG3 在包括胶质母细胞瘤(GBM)在内的多种肿瘤实体中发挥着多向致癌功能。在这里,我们比较了粘附培养或干样培养的 U251 GBM 细胞中 BAG3 蛋白与蛋白之间的相互作用。与BAG3在调控干样特性中的假定作用相一致,在球状培养细胞中鉴定出的相互作用者包括不同的干细胞标记物(SOX2、OLIG2和NES),而粘附的BAG3缺陷细胞的相互作用组表明BAG3转向参与调控纤毛组装(ACTR3和ARL3)。我们利用一组BAG3缺失构建物证明,在U251和U343细胞中,全长BAG3抑制纤毛形成时,除WW结构域外,其他结构域都不是必需的。根据该结构域对Hippo通路的既定调控,我们可以证明WW突变体不能挽救YAP1的核转位。BAG3 缺失减少了 YAP1/AURKA 信号通路的激活和 PLK1 的诱导。总之,我们的研究结果表明,BAG3 与调控纤毛稳态的几种途径之间存在复杂的相互作用网络,涉及纤毛发生和纤毛降解的相关过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

BAG3 regulates cilia homeostasis of glioblastoma via its WW domain.

BAG3 regulates cilia homeostasis of glioblastoma via its WW domain.
The multidomain protein BAG3 exerts pleiotropic oncogenic functions in many tumor entities including glioblastoma (GBM). Here, we compared BAG3 protein-protein interactions in either adherently cultured or stem-like cultured U251 GBM cells. In line with BAG3's putative role in regulating stem-like properties, identified interactors in sphere-cultured cells included different stem cell markers (SOX2, OLIG2, and NES), while interactomes of adherent BAG3-proficient cells indicated a shift toward involvement of BAG3 in regulation of cilium assembly (ACTR3 and ARL3). Applying a set of BAG3 deletion constructs we could demonstrate that none of the domains except the WW domain are required for suppression of cilia formation by full-length BAG3 in U251 and U343 cells. In line with the established regulation of the Hippo pathway by this domain, we could show that the WW mutant fails to rescue YAP1 nuclear translocation. BAG3 depletion reduced activation of a YAP1/AURKA signaling pathway and induction of PLK1. Collectively, our findings point to a complex interaction network of BAG3 with several pathways regulating cilia homeostasis, involving processes related to ciliogenesis and cilium degradation.
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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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