Pearce Michael J, Mintseris Julian, Ferreyra Jessica, Gygi Steven P, Darwin K Heran
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Science. 2008 Nov 14;322(5904):1104-7. doi: 10.1126/science.1163885. Epub 2008 Oct 2.
The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on lysines and required proteasome accessory factor A (PafA). In a pafA mutant, pupylated proteins were absent and substrates accumulated, thereby connecting pupylation with degradation. Although analogous to ubiquitylation, pupylation appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may use a small-protein modifier to control protein stability.
蛋白质修饰因子泛素是真核生物中蛋白酶体介导的蛋白质降解信号。人们一直认为带有蛋白酶体的原核生物通过不依赖泛素的途径降解蛋白质。我们鉴定出一种原核生物类泛素蛋白Pup（Rv2111c），它在病原体结核分枝杆菌中特异性地与蛋白酶体底物结合。Pup化发生在赖氨酸上，并且需要蛋白酶体辅助因子A（PafA）。在pafA突变体中，不存在Pup化蛋白且底物积累，从而将Pup化与降解联系起来。尽管Pup化类似于泛素化，但它似乎通过不同的化学过程进行。因此，与真核生物一样，细菌可能利用一种小蛋白质修饰因子来控制蛋白质稳定性。
