Proapoptotic Bcl-2 relative bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity
Proapoptotic Bcl-2 relative bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity
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DOI：
10.1126/science.286.5445.1735
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发表时间：
1999-11-26
期刊：
影响因子：
56.9
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Bouillet, P;Metcalf, D;Strasser, A
细胞凋亡可以由Bcl-2蛋白家族的成员触发，例如Bim，其仅与该家族共享BH 3结构域。在小鼠中的基因打靶揭示了sim的重要生理学意义。类红细胞和髓样细胞积聚，T细胞发育受到干扰，大多数老年小鼠积聚浆细胞并死于自身免疫性肾病。淋巴细胞对细胞因子剥夺、钙离子流和微管扰动等凋亡刺激不敏感，但对其他刺激不敏感。因此，Bim是造血稳态所需的，并作为自身免疫的屏障。此外，特定的死亡刺激似乎通过不同的BH 3-only蛋白激活细胞凋亡。
Apoptosis can be triggered by members of the Bcl-2 protein family, such as Bim, that share only the BH3 domain with this family. Gene targeting in mice revealed important physiological lores for sim. Lymphoid and myeloid cells accumulated, T cell development was perturbed, and most older mice accumulated plasma cells and succumbed to autoimmune kidney disease. Lymphocytes were refractory to apoptotic stimuli such as cytokine deprivation, calcium ion flux, and microtubule perturbation but not to others. Thus, Bim is required for hematopoietic homeostasis and as a barrier to autoimmunity. Moreover, particular death stimuli appear to activate apoptosis through distinct BH3-only proteins.