Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, UK.
Oncogene. 2011 May 26;30(21):2391-400. doi: 10.1038/onc.2010.636. Epub 2011 Feb 7.
Bax inhibitor 1 (BI-1) was originally discovered as an inhibitor of Bax-induced apoptosis; this review highlights the fundamental importance of BI-1 in a wider context, including in tissue homeostasis and as a regulator of cellular stress. BI-1 has been shown to interact with a broad range of partners to inhibit many facets of apoptosis, such as reactive oxygen species production, cytosolic acidification and calcium levels as well as endoplasmic reticulum stress signalling pathways. BI-1's anti-apoptotic action initially enables the cell to adapt to stress, although if the stress is prolonged or severe the actions of BI-1 may promote apoptosis. This almost universal anti-apoptotic capacity has been shown to be manipulated during infection with enteropathogenic and enterohaemorrhagic Escherichia coli inhibiting host cell death through direct interaction between their effector NleH and BI-1. In addition, BI-1 activity is important in a large number of cancers, promoting metastasis by modulating actin dynamics, a process dependent upon the BI-1 C-terminus and BI-1:actin interaction. Manipulation of BI-1 therefore has the potential for significant therapeutic benefit in a wide range of human diseases.
Bax 抑制剂 1（BI-1）最初被发现是 Bax 诱导细胞凋亡的抑制剂；本综述强调了 BI-1 在更广泛的背景下的重要性，包括在组织稳态和作为细胞应激调节剂中的作用。BI-1 已被证明与广泛的伴侣相互作用，以抑制细胞凋亡的许多方面，如活性氧的产生、细胞质酸化和钙水平以及内质网应激信号通路。BI-1 的抗细胞凋亡作用最初使细胞能够适应应激，尽管如果应激持续或严重，BI-1 的作用可能会促进细胞凋亡。这种几乎普遍的抗细胞凋亡能力已被证明在与肠致病性和肠出血性大肠杆菌的感染过程中被操纵，通过其效应蛋白 NleH 和 BI-1 之间的直接相互作用抑制宿主细胞死亡。此外，BI-1 在大量癌症中也很重要，通过调节肌动蛋白动力学促进转移，这一过程依赖于 BI-1 的 C 末端和 BI-1:肌动蛋白相互作用。因此，BI-1 的操纵有可能在广泛的人类疾病中带来显著的治疗益处。
