Co-translational processing of pro-ubiquitin

描述 泛素结构域的翻译后连接产生靶向 将修饰的蛋白质定位到蛋白酶体、细胞核、 细胞骨架和自噬系统。至少有五种不同的蛋白质 已知具有泛素结构域并将修饰的蛋白质靶向不同的 手机定位已经表明，聚合物的积累 去泛素化酶突变引起的泛素干扰了 将多聚泛素化蛋白质靶向蛋白酶体， 降解多聚体泛素也可以作为翻译的结果出现 proubiquitin的mRNA。该基因编码泛素的串联重复序列 结构域，并且产生的多蛋白必须通过以下步骤加工成单体： 在泛素的成熟C末端进行蛋白水解切割。最后， 泛素融合蛋白也在真核细胞中产生，这些蛋白必须 在泛素的C-末端被加工以释放泛素， 核糖体生物发生所需的C-末端融合蛋白， 功能很可能细胞必须避免产生聚合物， 泛素从这些基因，以防止干扰复杂的代谢 翻译后的泛素化。基于这种期望， 我们从未观察到前泛素蛋白， 假设前泛素基因产物的加工是 共翻译此外，我们怀疑这条消息的翻译是 周期性地停止以允许加工酶的募集， 这种停滞是由于每个拷贝中存在低丰度密码子 泛素编码序列这里提出的实验将检查这些 假设和进一步定义共翻译加工事件。

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.