Identification of a polymorphism in the RING finger of human Bmi-1 that causes its degradation by the ubiquitin-proteasome system.

Identification of a polymorphism in the RING finger of human Bmi-1 that causes its degradation by the ubiquitin-proteasome system.
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DOI:
10.1016/j.febslet.2009.02.023
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发表时间:
2009-03-18
期刊:
影响因子:
3.5
通讯作者:
Sarge, Kevin D.
Sarge, Kevin D.
中科院分区:
生物学3区
文献类型:
--
作者:
Zhang, Jie;Sarge, Kevin D.

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Bmi-1是一种多梳蛋白,在肿瘤细胞发育和维持许多细胞系的干细胞群中起重要作用。在这里,我们确定了人类Bmi-1的多态性,将其环结构域中的半胱氨酸改变为酪氨酸。这种C18Y多态性与Bmi-1水平的显著下降及其泛素化的升高有关,表明它正在被泛素-蛋白酶体系统破坏。与此一致的是,用蛋白酶体抑制剂MG-132处理细胞可显著增加C18Y Bmi-1水平。这是第一个Bmi-1多态性降低这种重要蛋白质水平的例子。
Bmi-1 is a polycomb protein that plays an important role in tumor cell development and maintaining stem cell populations of many cell lineages. Here we identify a polymorphism in human Bmi-1 that changes a cysteine within its RING domain to tyrosine. This C18Y polymorphism is associated with a significant decrease in Bmi-1 level and its elevated ubiquitination, suggesting that it is being destroyed by the ubiquitin-proteasome system. Consistent with this, treating cells with the proteasome inhibitor MG-132 significantly increases C18Y Bmi-1 levels. This is the first example of a polymorphism in Bmi-1 that reduces levels of this important protein.
DOI: 10.1038/ng.165
发表时间: 2008-07-01
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