Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma
Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma
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DOI：
10.1073/pnas.1217271110
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发表时间：
2013-03-05
影响因子：
11.1
通讯作者：
Staudt, Louis M.
中科院分区：
文献类型：
--
作者：
Chiorazzi, Michael;Rui, Lixin;Staudt, Louis M.
细胞死亡是一种常见的后生动物细胞的命运，其失活是人类恶性肿瘤的核心。在秀丽隐杆线虫中，在EGL-1/BH 3-only蛋白与抗凋亡CED-9/BCL 2蛋白结合后，通过激活半胱天冬酶CED-3发生凋亡性细胞死亡。在这里，我们报告了一个主要的替代机制，半胱天冬酶激活在体内涉及的F-盒蛋白DRE-1。DRE-1与EGL-1平行发挥作用，需要CED-9才能发挥活性，并与CED-9结合，这表明DRE-1通过灭活CED-9促进细胞凋亡。FBXO 10是一种与DRE-1相关的人类蛋白质，可结合BCL 2并促进其降解，从而引发细胞死亡。此外，一些人弥漫性大B细胞淋巴瘤在FBXO 10中具有失活突变或以低水平表达FBXO 10。我们的研究结果表明，DRE-1/FBXO 10是一个保守的调节细胞凋亡。
Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.