BACKGROUND & AIMS:
:Ubiquitylation plays multiple roles not only in proteasome-mediated protein degradation but also in various other cellular processes including DNA repair, signal transduction, and endocytosis. Ubiquitylation is mediated by ubiquitin ligases, which are predicted to be encoded by more than 600 genes in humans. RING finger (RNF) proteins form the majority of these ubiquitin ligases. It has also been predicted that there are 49 RNF proteins containing transmembrane regions in humans, several of which are specifically localized to membrane compartments in the secretory and endocytic pathways. Of these, RNF183, RNF186, RNF182, and RNF152 are closely related genes with high homology. These genes share a unique common feature of exhibiting tissue-specific expression patterns, such as in the kidney, nervous system, and colon. The products of these genes are also reported to be involved in various diseases such as cancers, inflammatory bowel disease, Alzheimer's disease, and chronic kidney disease, and in various biological functions such as apoptosis, endoplasmic reticulum stress, osmotic stress, nuclear factor-kappa B (NF-κB), mammalian target of rapamycin (mTOR), and Notch signaling. This review summarizes the current knowledge of these tissue-specific ubiquitin ligases, focusing on their physiological roles and significance in diseases.
背景与目标:
泛素化不仅在蛋白酶体介导的蛋白质降解中起着多种作用,而且在包括DNA修复,信号转导和内吞作用在内的各种其他细胞过程中也起着多种作用。泛素化是由泛素连接酶介导的,据预测,泛素连接酶是由人类600多个基因编码的。无名指(RNF)蛋白形成了这些泛素连接酶的大部分。还已经预测在人中有49个RNF蛋白含有跨膜区域,其中一些特异地定位于分泌和内吞途径中的膜区室。其中,RNF183,RNF186,RNF182和RNF152是高度同源的密切相关的基因。这些基因具有独特的共同特征,表现出组织特异性表达模式,例如在肾脏,神经系统和结肠。这些基因的产物还据报道涉及多种疾病,例如癌症,炎性肠病,阿尔茨海默氏病和慢性肾脏病,以及多种生物学功能,例如细胞凋亡,内质网应激,渗透压应激,核因子-κ B(NF-κB),雷帕霉素(mTOR)的哺乳动物靶标和Notch信号转导。这篇综述总结了这些组织特异性泛素连接酶的当前知识,重点是它们在疾病中的生理作用和意义。