scholarly journals Role of Ring Finger Protein 213 in Moyamoya Disease

2016 ◽  
Vol 129 (20) ◽  
pp. 2497-2501 ◽  
Author(s):  
Yong-Gang Ma ◽  
Qian Zhang ◽  
Le-Bao Yu ◽  
Ji-Zong Zhao
Keyword(s):  
Moyamoya Disease ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals Arkadia (RING Finger Protein 111) Mediates Sumoylation-Dependent Stabilization of Nrf2 Through K48-Linked Ubiquitination

2018 ◽  
Vol 46 (1) ◽  
pp. 418-430 ◽  
Author(s):  
Deneshia J. McIntosh ◽  
Treniqka S. Walters ◽  
Ifeanyi J. Arinze ◽  
Jamaine Davis
Keyword(s):  
Gene Transcription ◽  
Ring Finger ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Heme Oxygenase 1 ◽  
Ring Finger Protein ◽  
Whole Cell ◽  
Cell Lysates ◽  
Finger Protein

Background/Aims: The transcription factor Nrf2 is a master regulator of the antioxidant defense system, protecting cells from oxidative damage. We previously reported that the SUMO-targeted E3 ubiquitin ligase (STUbL), RING finger protein 4 (RNF4) accelerated the degradation rate of Nrf2 in promyelocytic leukemia-nuclear body (PML-NB)-enriched fractions and decreased Nrf2-mediated gene transcription. The mechanisms that regulate Nrf2 nuclear levels are poorly understood. In this study, we aim to explore the role of the second mammalian STUbL, Arkadia/RNF111 on Nrf2. Methods: Arkadia mediated ubiquitination was detected using co-immunoprecipitation assays in which whole cell lysates were immunoprecipated with anti-Nrf2 antibody and Western blotted with anti-hemagglutinin (HA) antibody or anti-Lys-48 ubiquitin-specific antibody. The half-life of Nrf2 was detected in whole cell lysates and promyelocytic leukemia-nuclear body enriched fractions by cycloheximide-chase. Reporter gene assays were performed using the antioxidant response element (ARE)-containing promoter Heme oxygenase-1 (HO-1). Results: We show that Arkadia/RNF111 is able to ubiquitinate Nrf2 resulting in the stabilization of Nrf2. This stabilization was mediated through Lys-48 ubiquitin chains, contrary to traditionally degradative role of Lys-48 ubiquitination, suggesting that Lys-48 ubiquitination of Nrf2 protects Nrf2 from degradation thereby allowing Nrf2-dependent gene transcription. Conclusion: Collectively, these findings highlight a novel mechanism to positively regulate nuclear Nrf2 levels in response to oxidative stress through Arkadia-mediated K48-linked ubiquitination of Nrf2.

scholarly journals Structural basis for role of ring finger protein RNF168 RING domain

Cell Cycle ◽  
2013 ◽  
Vol 12 (2) ◽  
pp. 312-321 ◽  
Author(s):  
Xiaoqin Zhang ◽  
Jie Chen ◽  
Minhao Wu ◽  
Huakai Wu ◽  
Aloysius Wilfred Arokiaraj ◽  
...  
Keyword(s):  
Ring Finger ◽  
Ring Domain ◽  
Structural Basis ◽  
Ring Finger Protein ◽  
Finger Protein

scholarly journals The Impact of Moyamoya Disease and RNF213 Mutations on the Spectrum of Plasma Protein and MicroRNA

2019 ◽  
Vol 8 (10) ◽  
pp. 1648 ◽  
Author(s):  
Ming-Jen Lee ◽  
Shannon Fallen ◽  
Yong Zhou ◽  
David Baxter ◽  
Kelsey Scherler ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Plasma Protein ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Absolute Quantitation ◽  
Small Vessels ◽  
Finger Protein ◽  
Isobaric Tags ◽  
Ischemic Attack ◽  
The Impact

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by occlusion of bilateral internal carotid and intracerebral arteries with the compensatory growth of fragile small vessels. MMD patients develop recurrent infarctions in the basal ganglia and subcortical regions. Symptoms include transient ischemic attack or stroke, seizures, and headaches, which may occur suddenly or in a stepwise progression. Mutations in Ring Finger Protein 213 (RNF213), a Zinc ring finger protein, have been identified in some MMD patients but the etiology of MMD is still largely unknown. To gain insight into the pathophysiology of MMD, we characterized the impact of the RNF213 mutations on plasma protein and RNA profiles. Isobaric tags for relative and absolute quantitation and proximity extension assay were used to characterize the plasma proteome. Next generation sequencing-based small RNAseq was used to analyze the cell-free small RNAs in whole plasma and RNA encapsulated in extracellular vesicles. The changes of miRNAs and proteins identified are associated with signaling processes including angiogenesis and immune activities which may reflect the pathology and progression of MMD.

Abstract WP280: Caveolin-1, Ring Finger Protein 213, and Endothelial Function in Moyamoya Disease

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jong-Won Chung ◽  
Suk Jae Kim ◽  
Jaechun Hwang ◽  
Mi Ji Lee ◽  
Hanna Choe ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Path Analysis ◽  
Moyamoya Disease ◽  
Susceptibility Gene ◽  
Ring Finger ◽  
Unknown Etiology ◽  
Ring Finger Protein ◽  
Protein Biomarkers ◽  
Caveolin 1 ◽  
Finger Protein

Background: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 (RNF213) was identified as a susceptibility gene for MMD in East Asian. However, the pathogenesis of MMD is still unclear. Methods: We prospectively analyzed clinical data for 139 patients with MMD (108 definite MMD, 31 probable MMD) and 61 patients with intracranial atherosclerotic stroke (ICAS), and 68 healthy subjects. We compared the genetic (RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor [VEGF] and receptor [VEGFR2], and antagonizing cytokine [endostatin]) and endothelial dysfunction (asymmetric dimethylarginine [ADMA], nitric oxide and its metabolites [nitrite and nitrate]), between patients with MMD and ICAS. We then performed the path analysis to evaluate whether a certain protein biomarker mediates the association the genetic and MMD. Results: Caveolin-1 level was decreased in patients with MMD and this level was markedly decreased in RNF213 variant carriers. Circulating factor such as VEGF and receptor were not different among the groups. Markers for endothelial dysfunction were significantly higher in patients with ICAS, but normal in MMD. The path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 level that led to MMD. The level of combined marker of MMD (caveolin-1) and ICAS (ADMA, marker for endothelial dysfunction) predicted MMD with a good sensitivity and specificity. Conclusions: Our results indicate that MMD is primarily caveolae disorder, dysregulation of endothelial vesicular trafficking and signal transduction, but not related to endothelial dysfunction or dysregulation of circulating cytokines.

Caveolin-1, Ring finger protein 213, and endothelial function in Moyamoya disease

2016 ◽  
Vol 11 (9) ◽  
pp. 999-1008 ◽  
Author(s):  
Oh Young Bang ◽  
Jong-Won Chung ◽  
Suk Jae Kim ◽  
Mi Jeong Oh ◽  
Soo Yoon Kim ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Path Analysis ◽  
Moyamoya Disease ◽  
Susceptibility Gene ◽  
Ring Finger ◽  
Unknown Etiology ◽  
Ring Finger Protein ◽  
Protein Biomarkers ◽  
Caveolin 1 ◽  
Finger Protein

Background Moyamoya disease is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 ( RNF213) was identified as a susceptibility gene for Moyamoya disease in East Asian countries. However, the pathogenesis of Moyamoya disease remains unclear. Methods We prospectively analyzed clinical data for 139 patients with Moyamoya disease (108 bilateral Moyamoya disease, 31 unilateral Moyamoya disease), 61 patients with intracranial atherosclerotic stroke, and 68 healthy subjects. We compared the genetic ( RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor (VEGF) and receptor (VEGFR2), and antagonizing cytokine (endostatin)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA), and nitric oxide and its metabolites (nitrite and nitrate)) between patients with Moyamoya disease and intracranial atherosclerotic stroke. We then performed path analysis to evaluate whether a certain protein biomarker mediates the association between genes and Moyamoya disease. Results Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Circulating factors such as VEGF and VEGFR2 did not differ among the groups. Markers for endothelial dysfunction were significantly higher in patients with intracranial atherosclerotic stroke but normal in those with Moyamoya disease. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. The level of combined marker of Moyamoya disease (caveolin-1) and intracranial atherosclerotic stroke (ADMA, an endothelial dysfunction marker) predicted Moyamoya disease with good sensitivity and specificity. Conclusion Our results suggest that Moyamoya disease is a caveolae disorder but is not related to endothelial dysfunction or dysregulation of circulating cytokines.

Sign in / Sign up

Export Citation Format

Share Document