The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Denmark.
The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Denmark.
Biochim Biophys Acta Gene Regul Mech. 2023 Jun;1866(2):194925. doi: 10.1016/j.bbagrm.2023.194925. Epub 2023 Feb 28.
A moonlighting protein is one, which carries out multiple, often wholly unrelated, functions. The RAD23 protein is a fascinating example of this, where the same polypeptide and the embedded domains function independently in both nucleotide excision repair (NER) and protein degradation via the ubiquitin-proteasome system (UPS). Hence, through direct binding to the central NER component XPC, RAD23 stabilizes XPC and contributes to DNA damage recognition. Conversely, RAD23 also interacts directly with the 26S proteasome and ubiquitylated substrates to mediate proteasomal substrate recognition. In this function, RAD23 activates the proteolytic activity of the proteasome and engages specifically in well-characterized degradation pathways through direct interactions with E3 ubiquitin-protein ligases and other UPS components. Here, we summarize the past 40 years of research into the roles of RAD23 in NER and the UPS.
兼职蛋白是指执行多种功能的蛋白，这些功能往往完全不相关。RAD23 蛋白就是一个很好的例子，同一条多肽和嵌入的结构域分别独立地参与核苷酸切除修复 (NER) 和通过泛素-蛋白酶体系统 (UPS) 的蛋白质降解。因此，RAD23 通过直接与中央 NER 成分 XPC 结合，稳定 XPC 并有助于 DNA 损伤识别。相反，RAD23 还直接与 26S 蛋白酶体和泛素化底物相互作用，以介导蛋白酶体底物识别。在这个功能中，RAD23 激活蛋白酶体的蛋白水解活性，并通过与 E3 泛素-蛋白连接酶和其他 UPS 成分的直接相互作用，专门参与特征明确的降解途径。在这里，我们总结了过去 40 年来 RAD23 在 NER 和 UPS 中的作用的研究。
