Novel Multifaceted Roles for RNF213 Protein.
Novel Multifaceted Roles for RNF213 Protein.
复制标题
DOI：
10.3390/ijms23094492
复制
发表时间：
2022-04-19
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
环指蛋白213（RNF213），也称为Mysterin，是Moyamoya动脉病（MA）的主要易感因素，MA是一种进行性脑血管疾病，通常导致成人和儿童脑卒中。虽然已经报道了几种罕见的RNF213多态性，但迄今为止在高加索患者中尚未发现主要的易感性变体，因此无法确定MA治疗的假定治疗靶点。基于这些原因，对RNF213的新的生化功能、底物和未知伙伴的研究将有助于揭示MA的致病机制，并将有助于将来在诊断背景下对变异体的解释。本综述的目的是讨论新的角度来看，新兴的RNF213的作用，在最近的文献更新和剖析其相关性的理解MA和未来的研究设计。自其被鉴定以来，RNF213参与血管生成和血管发生的作用以及其在炎症信号和增殖途径中的作用已经加强。最近的研究越来越多地集中在其抗菌活性和脂质代谢的相关性，突出了新的有趣的观点。最后一个领域可能表明RNF213在蛋白酶体途径中的主要作用，从而加强了先前已经制定的假设，该假设将蛋白质描述为参与血管生成的客户蛋白质稳定性的重要调节剂。我们认为，本文综述的新证据可能有助于解开MA复杂且仍不清楚的发病机制，这反映在缺乏能够减缓或阻止疾病进展和严重程度的治疗。
Ring Finger Protein 213 (RNF213), also known as Mysterin, is the major susceptibility factor for Moyamoya Arteriopathy (MA), a progressive cerebrovascular disorder that often leads to brain stroke in adults and children. Although several rare RNF213 polymorphisms have been reported, no major susceptibility variant has been identified to date in Caucasian patients, thus frustrating the attempts to identify putative therapeutic targets for MA treatment. For these reasons, the investigation of novel biochemical functions, substrates and unknown partners of RNF213 will help to unravel the pathogenic mechanisms of MA and will facilitate variant interpretations in a diagnostic context in the future. The aim of the present review is to discuss novel perspectives regarding emerging RNF213 roles in light of recent literature updates and dissect their relevance for understanding MA and for the design of future research studies. Since its identification, RNF213 involvement in angiogenesis and vasculogenesis has strengthened, together with its role in inflammatory signals and proliferation pathways. Most recent studies have been increasingly focused on its relevance in antimicrobial activity and lipid metabolism, highlighting new intriguing perspectives. The last area could suggest the main role of RNF213 in the proteasome pathway, thus reinforcing the hypotheses already previously formulated that depict the protein as an important regulator of the stability of client proteins involved in angiogenesis. We believe that the novel evidence reviewed here may contribute to untangling the complex and still obscure pathogenesis of MA that is reflected in the lack of therapies able to slow down or halt disease progression and severity.
登录
查看更多内容
影响因子：
5.8
作者：
Kimmey JM;Campbell JA;Weiss LA;Monte KJ;Lenschow DJ;Stallings CL
通讯作者：
Stallings CL
影响因子：
4
作者：
Guey, Stephanie;Grangeon, Lou;Kossorotoff, Manoelle
通讯作者：
Kossorotoff, Manoelle
影响因子：
8.3
作者：
Cecchi AC;Guo D;Ren Z;Flynn K;Santos-Cortez RL;Leal SM;Wang GT;Regalado ES;Steinberg GK;Shendure J;Bamshad MJ;University of Washington Center for Mendelian Genomics;Grotta JC;Nickerson DA;Pannu H;Milewicz DM
通讯作者：
Milewicz DM
影响因子：
4.9
作者：
Kiando, Soto Romuald;Barlassina, Cristina;Bouatia-Naji, Nabila
通讯作者：
Bouatia-Naji, Nabila
影响因子：
3.7
作者：
BAZZIGHER, L;PAVLOVIC, J;STAEHELI, P
通讯作者：
STAEHELI, P