scholarly journals Essential Role of the E3 Ubiquitin Ligase NOPPERABO1 in Schizogenous Intercellular Space Formation in the Liverwort Marchantia polymorpha

2013 ◽  
Vol 25 (10) ◽  
pp. 4075-4084 ◽  
Author(s):  
Kimitsune Ishizaki ◽  
Miya Mizutani ◽  
Masaki Shimamura ◽  
Akihide Masuda ◽  
Ryuichi Nishihama ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Intercellular Space ◽  
Essential Role ◽  
E3 Ubiquitin Ligase ◽  
Marchantia Polymorpha

scholarly journals Essential Role of the E3 Ubiquitin Ligase Cbl-b in T Cell Anergy Induction

Immunity ◽  
2004 ◽  
Vol 21 (2) ◽  
pp. 167-177 ◽  
Author(s):  
Myung-Shin Jeon ◽  
Alex Atfield ◽  
K. Venuprasad ◽  
Connie Krawczyk ◽  
Renu Sarao ◽  
...  
Keyword(s):  
T Cell ◽  
Ubiquitin Ligase ◽  
Essential Role ◽  
E3 Ubiquitin Ligase ◽  
T Cell Anergy ◽  
Cell Anergy

scholarly journals Essential Role of E3 Ubiquitin Ligase Activity in Cbl-b–Regulated T Cell Functions

2011 ◽  
Vol 186 (4) ◽  
pp. 2138-2147 ◽  
Author(s):  
Magdalena Paolino ◽  
Christine B. F. Thien ◽  
Thomas Gruber ◽  
Reinhard Hinterleitner ◽  
Gottfried Baier ◽  
...  
Keyword(s):  
T Cell ◽  
Ubiquitin Ligase ◽  
Essential Role ◽  
E3 Ubiquitin Ligase ◽  
Cell Functions ◽  
Ubiquitin Ligase Activity

scholarly journals E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis

2021 ◽  
Author(s):  
Yuhua Shi ◽  
Yang Yang ◽  
Weilv Xu ◽  
Wei Xu ◽  
Xinyu Fu ◽  
...  
Keyword(s):  
Cell Death ◽  
Ubiquitin Ligase ◽  
Essential Role ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
E3 Ubiquitin Ligase ◽  
Positive Regulator ◽  
Ldh Release

Gasdermin D (GSDMD) participates in activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D is regulated through ubiquitination. Specifically, SYVN1, an E3 ubiquitin ligase of gasdermin D, promotes GSDMD-mediated pyroptosis. SYVN1 deficiency inhibits pyroptosis and subsequent LDH release and PI uptake. SYVN1 directly interacts with GSDMD, and mediates K27-linked polyubiquitination of GSDMD on K203 and K204 residues, promoting GSDMD-induced pyroptotic cell death. Thus, our findings revealed the essential role of SYVN1 in GSDMD-mediated pyroptosis. Overall, GSDMD ubiquitination is a potential therapeutic module for inflammatory diseases.

Activation mechanisms of the E3 ubiquitin ligase parkin

2017 ◽  
Vol 474 (18) ◽  
pp. 3075-3086 ◽  
Author(s):  
Nikhil Panicker ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Recent Literature ◽  
E3 Ubiquitin Ligase ◽  
Mitochondrial Damage ◽  
Cytosolic Protein ◽  
Mitochondrial Functions ◽  
Activation Mechanisms

Monogenetic, familial forms of Parkinson's disease (PD) only account for 5–10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.

Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
James L. Shen ◽  
Tina M. Fortier ◽  
Ruoxi Wang ◽  
Eric H. Baehrecke
Keyword(s):  
Neurodegenerative Diseases ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Mitochondrial Morphology ◽  
The Core ◽  
Mitochondrial Defects ◽  
Mutant Cells

Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.

scholarly journals Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

2020 ◽  
Vol 11 (14) ◽  
pp. 4007-4014
Author(s):  
Zhao-Ru Dong ◽  
Wei Zhou ◽  
Dong Sun ◽  
Yu-Chuan Yan ◽  
Chun-Cheng Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase

scholarly journals Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy

2019 ◽  
Vol 218 (3) ◽  
pp. 798-807 ◽  
Author(s):  
Victoria Riccio ◽  
Nicholas Demers ◽  
Rong Hua ◽  
Miluska Vissa ◽  
Derrick T. Cheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ubiquitin Ligase ◽  
Cell Function ◽  
E3 Ubiquitin Ligase ◽  
Metabolic Stress ◽  
Amino Acid Starvation ◽  
Deubiquitinating Enzyme ◽  
Potential Therapeutic Target ◽  
Autophagic Degradation

The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction under basal conditions. We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2. Finally, we show that USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target.

scholarly journals TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis

2019 ◽  
Vol 121 (12) ◽  
pp. 1069-1078 ◽  
Author(s):  
Guanghui Zhang ◽  
Qingzong Zhu ◽  
Gang Fu ◽  
Jianbing Hou ◽  
Xiaosong Hu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Therapeutic Target ◽  
Biological Effect ◽  
Thyroid Hormone Receptor ◽  
E3 Ubiquitin Ligase ◽  
Mitotic Checkpoint ◽  
Migration And Invasion ◽  
Cell Models ◽  
Aaa Atpase

Abstract Background Thyroid hormone receptor interactor 13 (TRIP13) is an AAA + ATPase that plays an important role in the mitotic checkpoint. TRIP13 is highly expressed in various human tumours and promotes tumorigenesis. However, the biological effect of TRIP13 in GBM cells remains unclear. Methods We generated GBM cell models with overexpressed or silenced TRIP13 via lentivirus-mediated overexpression and RNAi methods. The biological role of TRIP13 in the proliferation, migration and invasion of GBM cells has been further explored. Results Our research indicated that TRIP13 was highly expressed in GBM tissues and cells. We found that the proliferation, migration and invasion abilities were inhibited in TRIP13-knockdown GBM cells. These results indicated that TRIP13 plays an important role in the tumorigenesis of GBM. Moreover, we found that TRIP13 first stabilised c-MYC by inhibiting the transcription of FBXW7, which is an E3 ubiquitin ligase of c-MYC, by directly binding to the promoter region of FBXW7. Therefore, our study indicated that the TRIP13/FBXW7/c-MYC pathway might provide a prospective therapeutic target in the treatment of GBM. Conclusions These results indicated that TRIP13 plays an oncogenic role in GBM. The TRIP13/FBXW7/c-MYC pathway might act as a prospective therapeutic target for GBM patients.

scholarly journals p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex

2017 ◽  
Vol 37 (8) ◽  
Author(s):  
Shasha Tao ◽  
Pengfei Liu ◽  
Gang Luo ◽  
Montserrat Rojo de la Vega ◽  
Heping Chen ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Protein Complexes ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Proteasome System ◽  
Proteasomal Degradation ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Proteasome ◽  
Client Proteins

ABSTRACT Activation of the stress-responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and is targeted to the proteasome for degradation (the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation was previously unknown. p97 is a ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system (UPS). In this study, we show that p97 negatively regulates NRF2 through the canonical pathway by extracting ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex, with the aid of the heterodimeric cofactor UFD1/NPL4 and the UBA-UBX-containing protein UBXN7, for efficient proteasomal degradation. Given the role of NRF2 in chemoresistance and the surging interest in p97 inhibitors to treat cancers, our results indicate that dual p97/NRF2 inhibitors may offer a more potent and long-term avenue of p97-targeted treatment.

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