Co-translational processing of pro-ubiquitin

描述 泛素结构域的翻译后附着产生靶向 将修饰的蛋白质定位于蛋白酶体、核、 细胞骨架和自噬系统。至少有五种不同的蛋白质是 已知具有泛素结构域和靶向修饰蛋白的不同 蜂窝位置。研究表明，聚合体的积累 脱泛素化酶突变引起的泛素干扰 多泛素化蛋白靶向蛋白酶体，从而靶向蛋白质 退化。聚合泛素也可以作为翻译的结果而出现 泛素原信使核糖核酸。该基因编码泛素的串联重复序列 结构域，以及所产生的多蛋白必须通过 泛素成熟C-末端的蛋白水解性切割。最后， 泛素融合蛋白也在真核细胞中产生，这些必须 在泛素的C末端被加工以释放泛素和 核糖体生物发生所需的C末端融合蛋白和 功能。很可能细胞将不得不避免产生聚合物 来自这些基因的泛素，以防止干扰复杂的代谢 翻译后泛素化。基于这一预期， 观察到，我们从未观察到泛素原蛋白 假设泛素原基因产物的加工是 共同翻译。此外，我们怀疑这条消息的翻译是 周期性地停滞以允许处理酶的补充，并且 这种停滞是由于在每个拷贝中都存在低丰度密码子 泛素编码序列。这里提出的实验将检验这些 假设，并进一步定义协译处理事件。

DESCRIPTION The post-translational attachment of the ubiquitin domain generates a targeting signal that localizes modified proteins to the proteasome, the nucleus, the cytoskeleton and the autophagic system. At least five distinct proteins are known to possess the ubiquitin domain and target modified proteins to different cellular locations. It has been shown that the accumulation of polymeric ubiquitin caused by mutation of deubiquitinating enzymes interferes with the targeting of polyubiquitinated proteins to the proteasome and thus, protein degradation. Polymeric ubiquitin can also arise as a result of the translation of the proubiquitin mRNA. This gene codes for tandem repeats of the ubiquitin domain, and the polyprotein that results must be processed to the monomer by proteolytic cleavage at the mature C-terminus of ubiquitin.Finally, ubiquitin-fusion proteins are also produced in eukaryotic cells and these must be processed at the C-terminus of ubiquitin to release ubiquitin and the C-terminal fusion proteins that are required for ribosome biogenesis and function. It is likely that the cell would have to avoid producing polymeric ubiquitin from these genes to prevent interference with the complex metabolism of post-translational ubiquitination. Based on this expectation, and the observation that the pro-ubiquitin protein is never observed we have hypothesized that processing of the pro-ubiquitin gene product is co-translational. Further, we suspect that the translation of this message is periodically stalled to allow recruitment of the processing enzyme and that this stalling is due to the presence of low abundance codons in each copy of ubiquitin coding sequence. Experiments proposed here will examine these hypotheses and further define cotranslational processing events.