Corelating the molecular structure of BAG3 to its oncogenic role

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-06-23 DOI:10.1002/cbin.12199

Tabinda Showkat Pattoo, Firdous A. Khanday

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Abstract

BAG3 is a multifaceted protein characterised by having WW domain, PXXP motif and BAG domain. This protein gets upregulated during malignant transformation of cells and has been associated with poorer survival of patients. Procancerous activity of BAG domain of BAG3 is well documented. BAG domain interacts with ATPase domain of Hsp-70 preventing protein delivery to proteasome. This impediment results in enhanced cell survival, proliferation, resistance to apoptosis and chemoresistance. Besides BAG domain other two domains/motifs of BAG3 are under research vigilance to explore its further oncogenic role. This review summarises the role of different structural determinants of BAG3 in elevating oncogenesis. Based on the already existing findings, more interacting partners of BAG3 are anticipated. The anticipated partners of BAG3 can shed a wealth of information into the mechanistic insights of its proproliferative role. Proper insights into the mechanistic details adopted by BAG3 to curtail/elaborate activity of anticipated interacting partners can serve as a potent target for development of therapeutic interventions.

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将 BAG3 的分子结构与其致癌作用联系起来。

BAG3 是一种具有 WW 结构域、PXXP 矩阵和 BAG 结构域的多层面蛋白质。这种蛋白质在细胞恶性转化过程中上调，并与患者存活率较低有关。BAG3 的 BAG 结构域具有抗癌活性。BAG 结构域与 Hsp-70 的 ATPase 结构域相互作用，阻止蛋白质向蛋白酶体输送。这种障碍会导致细胞存活、增殖、抗凋亡和抗化疗能力增强。除 BAG 结构域外，BAG3 的其他两个结构域/基团也在研究中，以探索其进一步的致癌作用。本综述总结了 BAG3 的不同结构决定因素在促进肿瘤发生中的作用。根据已有的研究结果，预计 BAG3 会有更多的相互作用伙伴。预期的 BAG3 伴侣可为深入了解其增殖作用的机理提供丰富的信息。适当了解 BAG3 削弱/加强预期相互作用伙伴活性的机制细节，可作为开发治疗干预措施的有效靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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