Ubiquitin-Konjugat Bildung und Interaktion mit dem Proteasom (Ubiquitin Conjugate Formation and Proteasome Targeting)

通过泛素/蛋白酶体途径选择性地降解蛋白质，包括底物识别的泛素结合系统和降解的蛋白酶体。最近，我们发现了一种新的泛素化因子C4(UFD2)，它与E1、E2和E3酶协同介导多泛素化。E4与假定的伴侣CDC48相互作用，CDC48与其结合伙伴UNI2共同参与UFD(泛素融合)的降解。我们提出的研究的中心目标是确定这些因子的功能，并建立从底物泛素化到蛋白酶体降解的事件序列。

Selective protein degradation by the ubiquitin/proteasome pathway involves the ubiquitin-conjugation system for substrate recognition and the proteasome for degradation. Recently, we have identified a novel ubiquitination factor, C4 (UFD2), that mediates multiubiquitination in cooperation with E1, E2 and E3 enzymes. E4 interacts with the putative chaperone CDC48, which together with its binding partner UNI2 is required for UFD (ubiquitin fusion) degradation. The central objective of our proposed research is to define the functions of these factors and to establish the sequence of events which lead from the ubiquitination of a substrate to its degradation by the proteasome.