scholarly journals RNF6 as an Oncogene and Potential Therapeutic Target—A Review

BioTech ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 22
Author(s):  
Paweł Zapolnik ◽  
Antoni Pyrkosz
Keyword(s):  
Ubiquitin Ligase ◽  
Therapeutic Target ◽  
Human Cancer ◽  
Ring Finger ◽  
Model Organisms ◽  
Ring Finger Protein ◽  
Potential Therapeutic Target ◽  
Finger Protein ◽  
Potential Prognostic Factor

The RNF6 gene encodes Ring Finger Protein 6 (RNF6), which functions as a ubiquitin ligase. Its functions are not entirely known, but research shows that it is involved in human cancer development. Initially, this gene was considered to be a tumor suppressor. Numerous statistical analyses on cell lines and animals indicate, however, that RNF6 functions as an oncogene, involved in signaling pathways, including SHP1/STAT3, AKT/mTOR, Wnt/β-catenin, or ERα/Bcl-xL. Due to this fact, it has become a potential prognostic factor and therapeutic target. Studies in tumor cells and model organisms using inhibitors such as total saponins from Paris forrestii (TSPf), ellagic acid, or microRNA molecules show the effectiveness of inhibiting RNF6, and through it, the pathways of tumor cell proliferation. The results of the currently available studies are promising, but the function of RNF6 is not fully understood. More research is needed to assess the role of RNF6 and to check the safety and efficacy of inhibitors.

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 Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia

2011 ◽  
Vol 18 (9) ◽  
pp. 1500-1506 ◽  
Author(s):  
S S Devgan ◽  
O Sanal ◽  
C Doil ◽  
K Nakamura ◽  
S A Nahas ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Ataxia Telangiectasia ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein

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 A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4190
Author(s):  
Sylvie Morel ◽  
Gérald Hugon ◽  
Manon Vitou ◽  
Marie Védère ◽  
Françoise Fons ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cell ◽  
Ubiquitin Ligase ◽  
Human Skeletal Muscle ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Promoting Effect ◽  
Finger Protein ◽  
Human Skeletal Muscle Cells ◽  
Bioassay Guided Fractionation

A good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophy-promoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1.

scholarly journals Ring Finger Protein 149 Is an E3 Ubiquitin Ligase Active on Wild-type v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

2012 ◽  
Vol 287 (28) ◽  
pp. 24017-24025 ◽  
Author(s):  
Seung-Woo Hong ◽  
Dong-Hoon Jin ◽  
Jae-Sik Shin ◽  
Jai-Hee Moon ◽  
Young-Soon Na ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Wild Type ◽  
Viral Oncogene ◽  
Finger Protein ◽  
Type V ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

scholarly journals Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation

FEBS Letters ◽  
2011 ◽  
Vol 585 (24) ◽  
pp. 3856-3861 ◽  
Author(s):  
Bernhard Braun ◽  
Thorsten Pfirrmann ◽  
Ruth Menssen ◽  
Kay Hofmann ◽  
Hartmut Scheel ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
Ubiquitin Ligase Activity
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