Ustrell Vicença, Hoffman Laura, Pratt Gregory, Rechsteiner Martin
Department of Biochemistry, University of Utah, 50 N Medical Drive, Salt Lake City, UT 84132, USA.
EMBO J. 2002 Jul 1;21(13):3516-25. doi: 10.1093/emboj/cdf333.
We have identified a novel 200 kDa nuclear protein that activates the proteasome. The protein, which we call PA200, has been purified to homogeneity from bovine testis and has been shown to activate proteasomal hydrolysis of peptides, but not proteins. Following gamma-irradiation of HeLa cells the uniform nuclear distribution of PA200 changes to a strikingly punctate pattern, a behavior characteristic of many DNA repair proteins. Homologs of PA200 are present in worms, plants and yeast. Others have shown that mutation of yeast PA200 results in hypersensitivity to bleomycin, and exposure of yeast to DNA damaging agents induces the PA200 message. Taken together, these findings implicate PA200 in DNA repair, possibly by recruiting proteasomes to double strand breaks.
我们鉴定出一种能激活蛋白酶体的新型200 kDa核蛋白。这种我们称为PA200的蛋白已从牛睾丸中纯化至同质，并已证明它能激活蛋白酶体对肽而非蛋白质的水解作用。用γ射线照射HeLa细胞后，PA200在细胞核内的均匀分布会变为显著的点状模式，这是许多DNA修复蛋白的特征性行为。PA200的同源物存在于蠕虫、植物和酵母中。其他人已表明，酵母PA200的突变会导致对博来霉素超敏，并且将酵母暴露于DNA损伤剂会诱导PA200的信使。综上所述，这些发现表明PA200参与DNA修复，可能是通过将蛋白酶体募集到双链断裂处来实现的。
