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【转贴】细胞死亡的基本问题被回答
关键字：Bruce基因|p53
Bruce是编码一种能抑制细胞凋亡的蛋白的基因。最近的一项研究揭示出Bruce的先前不为人知的作用途径。Stowers研究所的Chunying Du博士等人将这些发现刊登在2005年1月18日的Proceedings of the National Academy of Sciences上。
一直以来，Bruce被认为是细胞凋亡的抑制剂，但到目前为止它的抑制途径却还不清楚。Du博士对Bruce突变小鼠进行了分析，并且发现Bruce能够调节P53基因以及凋亡的线粒体途径。
Bruce的基本功能位于线粒体的上游。Bruce功能的丧失会增加p53的水平，因此使细胞对凋亡更加敏感。P53在转录水平的活性是负责活化Pidd、Bax和Bak基因。这些基因顺次又活化线粒体，从而导致凋亡的发生。
Bruce对p53的调节功能的确定意味着人们或许能通过抑制Bruce的活性来保持较高水平的p53，从而达到抗击特定肿瘤的目的。另外，Bruce的过表达可能有助于维持神经退化疾病中的细胞存活。这些发现回答了凋亡的一个基本问题并且将对各种疾病的研究产生重要的影响。
The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development
Jinyu Ren *, Mingan Shi *, Renshui Liu *, Qi-Heng Yang , Teri Johnson *, William C. Skarnes , and Chunying Du *¶
*Stowers Institute for Medical Research, Kansas City, MO 64110; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160; and Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021
Communicated by Xiaodong Wang, University of Texas Southwestern Medical Center, Dallas, TX, November 29, 2004 (received for review October 26, 2004)
Baculoviral inhibitor of apoptosis repeat-containing (Birc)6 gene/BIRC6 (Bruce/APOLLON) encodes an inhibitor of apoptosis and a chimeric E2/E3 ubiquitin ligase in mammals. The physiological role of Bruce in antiapoptosis is unknown. Here, we show that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality. This apoptosis is associated with up-regulation and nuclear localization of the tumor suppressor p53 and activation of mitochondrial apoptosis, which includes up-regulation of Bax, Bak, and Pidd, translocation of Bax and caspase-2 onto mitochondria, release of cytochrome c and apoptosis-inducing factor, and activation of caspase-9 and caspase-3. Mutant mouse embryonic fibroblasts are sensitive to multiple
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作者:admin@医学,生命科学 2011-05-27 05:14
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