PDF(Pubmed)
Abstract：
Effective cancer therapy with limited adverse effects is a major challenge in the medical field. This is especially complicated by the development of acquired chemoresistance. Understanding the mechanisms that underlie these processes remains a major effort in cancer research. In this review, we focus on the dual role that Bid protein plays in apoptotic cell death via the mitochondrial pathway, in oncogenesis and in cancer therapeutics. The BH3 domain in Bid and the anti-apoptotic mitochondrial proteins (Bcl-2, Bcl-XL, mitochondrial ATR) it associates with at the outer mitochondrial membrane provides us with a viable target in cancer therapy. We will discuss the roles of Bid, mitochondrial ATR, and other anti-apoptotic proteins in intrinsic apoptosis, exploring how their interaction sustains cellular viability despite the initiation of upstream death signals. The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria.
摘要：
具有有限副作用的有效癌症治疗是医学领域的主要挑战。这对于获得性化学抗性的发展尤其复杂。了解这些过程背后的机制仍然是癌症研究的主要努力。在这次审查中,我们关注Bid蛋白通过线粒体途径在凋亡细胞死亡中的双重作用，在肿瘤发生和癌症治疗中。Bid中的BH3结构域和抗凋亡线粒体蛋白（Bcl-2，Bcl-XL，线粒体ATR）它与线粒体外膜相关，为我们提供了癌症治疗的可行靶标。我们将讨论投标的作用，线粒体ATR,和其他内在凋亡中的抗凋亡蛋白，探索尽管上游死亡信号的启动，它们的相互作用如何维持细胞活力。这种Bid蛋白在癌细胞中的意外上调也可能有助于解释获得性化学抗性背后的机制。tBid和抗凋亡线粒体ATR之间的线粒体上稳定的蛋白质缔合在维持癌细胞的生存能力中起着至关重要的作用。提示通过将tBid从线粒体的ATR关联中释放来诱导癌细胞凋亡的新机制。
