The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial, neuronal, and germ cells
The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial, neuronal, and germ cells
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DOI：
10.1016/s0002-9440(10)64557-9
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发表时间：
2000-08-01
影响因子：
6
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
O'Reilly, LA;Cullen, L;Strasser, A
促凋亡的Bcl-2家族成员通过中和抗凋亡的亲属来激活细胞死亡，进而通过调节细胞死亡效应因子的激活来维持细胞的活力，caspase，Bim属于一个不同的促凋亡蛋白亚群，仅在短的BH3结构域内与其他Bcl-2家族成员相似。小鼠的基因打靶实验表明，His对于某些但不是所有的凋亡刺激的执行，对于造血细胞的稳态，以及作为对抗自身免疫的屏障是必不可少的。有三种Bim亚型，Bim(S)、Bim(L)和Bim(EL)，它们具有不同的促凋亡能力，至少部分原因是与动力蛋白运动复合体相互作用的不同。通过免疫组织化学染色、免疫沉淀、Western blotting和原位杂交等方法研究Bim在造血细胞、上皮细胞、神经细胞和生殖细胞中的表达。在多种细胞类型中，Bim(L)和Bim(EL)共表达水平相近，但未检测到Bim(S)。镜下可见Bim(L)和Bim(EL)免疫组织化学染色呈点状，提示与细胞质结构有关。这些结果是在Bim缺陷小鼠的表型和Bim促凋亡活性的翻译后调节的背景下讨论的。
Proapoptotic Bcl-2 family members activate cell death by neutralizing their anti-apoptotic relatives, which in turn maintain cell viability by regulating the activation of the cell death effecters, the caspases, Bim belongs to a distinct subgroup of proapoptotic proteins that only resemble other Bcl-2 family members within the short BH3 domain. Gene targeting experiments in mice have shown that him is essential for the execution of some but not all apoptotic stimuli, for hematopoietic cell homeostasis, and as a barrier against autoimmunity. There are three Bim isoforms, Bim(S), Bim(L), and Bim(EL), which have different proapoptotic potencies due at least in part to differences in interaction with the dynein motor complex. The expression pattern of Bim was investigated by immunohistochemical staining, immunoprecipitation followed by Western blotting, and in situ hybridization, him was found in hematopoietic, epithelial, neuronal, and germ cells. Bim(L) and Bim(EL) were coexpressed at similar levels In many cell types, but Bim(S) was not detected. Microscopic examination revealed a punctate pattern of Bim(L) and Bim(EL) immunostaining, indicating association with cytoplasmic structures. These results are discussed in the context of the phenotype of Bim-deficient mice and the post-translational regulation of Bim's pro-apoptotic activity.