在细胞凋亡和自噬的十字路口：伴侣分子BAG3在癌症的应激和抗药性中的多重作用。,Cells

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在细胞凋亡和自噬的十字路口：伴侣分子BAG3在癌症的应激和抗药性中的多重作用。
Cells ( IF 5.1 ) Pub Date : 2020-02-28 , DOI: 10.3390/cells9030574
Donat Kögel _{1,

2} , Benedikt Linder ₁ , Andreas Brunschweiger ₃ , Silvia Chines ₃ , Christian Behl ₄

Affiliation

BAG3是一种多功能HSP70伴侣蛋白和抗凋亡蛋白，可通过其C端BAG结构域与HSP70的ATPase结构域相互作用，在细胞蛋白水解中起着关键的生理作用。HSP70 / BAG3复合物通过两种主要的蛋白质降解途径（即蛋白酶体降解和巨噬细胞自噬）来调节其选择性，从而决定了大量选择性客户蛋白质的水平。一方面，BAG3与BAG1竞争与HSP70的结合，从而防止其客户蛋白的蛋白酶体降解。通过在功能上与HSP70和LC3相互作用，BAG3还可以将多泛素化蛋白递送至自噬途径。BAG3发挥许多关键的生理功能，包括参与细胞应激反应，蛋白稳态，细胞死亡调控，发育，和细胞骨架动力学。相反，异常的BAG3功能/表达具有与心肌病，神经变性和癌症相关的病理生理相关性。近年来获得的证据强调了BAG3驱动癌症的几个关键特征，包括细胞粘附，转移，血管生成，增强的自噬活性和凋亡抑制这一事实。这篇综述提供了关于BAG3在癌症的应激和治疗抵抗中的作用的最新综述，特别着重于BAG3依赖性的凋亡信号转导和自噬/溶酶体活性的调节。包括细胞粘附，转移，血管生成，增强的自噬活性和凋亡抑制。这篇综述提供了关于BAG3在癌症的应激和治疗抵抗中的作用的最新综述，特别着重于BAG3依赖性的凋亡信号转导和自噬/溶酶体活性的调节。包括细胞粘附，转移，血管生成，增强的自噬活性和凋亡抑制。这篇综述提供了关于BAG3在癌症的应激和治疗抵抗中的作用的最新综述，特别着重于BAG3依赖性的凋亡信号转导和自噬/溶酶体活性的调节。

"点击查看英文标题和摘要"

At the Crossroads of Apoptosis and Autophagy: Multiple Roles of the Co-Chaperone BAG3 in Stress and Therapy Resistance of Cancer.

BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.

更新日期：2020-02-28

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