scholarly journals Roles of the ubiquitin ligase CUL4B and ADP-ribosyltransferase TiPARP in TCDD-induced nuclear export and proteasomal degradation of the transcription factor AHR

2021 ◽  
pp. 100886
Author(s):  
Mercedes Paz Rijo ◽  
Silvia Diani-Moore ◽  
Chenyi Yang ◽  
Pengbo Zhou ◽  
Arleen B. Rifkind
Keyword(s):  
Transcription Factor ◽  
Ubiquitin Ligase ◽  
Nuclear Export ◽  
Proteasomal Degradation ◽  
Adp Ribosyltransferase

Dual regulation of transcription factor Nrf2 by Keap1 and by the combined actions of β-TrCP and GSK-3

2015 ◽  
Vol 43 (4) ◽  
pp. 611-620 ◽  
Author(s):  
John D. Hayes ◽  
Sudhir Chowdhry ◽  
Albena T. Dinkova-Kostova ◽  
Calum Sutherland
Keyword(s):  
Transcription Factor ◽  
Growth Factors ◽  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Proteasomal Degradation ◽  
Regulation Of Transcription ◽  
Related Factor ◽  
Nrf2 Target Gene ◽  
The Stability

Nuclear factor-erythroid 2 p45 (NF-E2 p45)-related factor 2 (Nrf2) is a master regulator of redox homoeostasis that allows cells to adapt to oxidative stress and also promotes cell proliferation. In this review, we describe the molecular mechanisms by which oxidants/electrophilic agents and growth factors increase Nrf2 activity. In the former case, oxidants/electrophiles increase the stability of Nrf2 by antagonizing the ability of Kelch-like ECH-associated protein 1 (Keap1) to target the transcription factor for proteasomal degradation via the cullin-3 (Cul3)–RING ubiquitin ligase CRLKeap1. In the latter case, we speculate that growth factors increase the stability of Nrf2 by stimulating phosphoinositide 3-kinase (PI3K)−protein kinase B (PKB)/Akt signalling, which in turn results in inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3) and in doing so prevents the formation of a DSGIS motif-containing phosphodegron in Nrf2 that is recognized by the β-transducin repeat-containing protein (β-TrCP) Cul1-based E3 ubiquitin ligase complex SCFβ-TrCP. We present data showing that in the absence of Keap1, the electrophile tert-butyl hydroquinone (tBHQ) can stimulate Nrf2 activity and induce the Nrf2-target gene NAD(P)H:quinone oxidoreductase-1 (NQO1), whilst simultaneously causing inhibitory phosphorylation of GSK-3β at Ser9. Together, these observations suggest that tBHQ can suppress the ability of SCFβ-TrCP to target Nrf2 for proteasomal degradation by increasing PI3K−PKB/Akt signalling. We also propose a scheme that explains how other protein kinases that inhibit GSK-3 could stimulate induction of Nrf2-target genes by preventing formation of the DSGIS motif-containing phosphodegron in Nrf2.

scholarly journals The E3 Ubiquitin Ligase Thyroid Hormone Receptor-interacting Protein 12 Targets Pancreas Transcription Factor 1a for Proteasomal Degradation

2014 ◽  
Vol 289 (51) ◽  
pp. 35593-35604 ◽  
Author(s):  
Naïma Hanoun ◽  
Samuel Fritsch ◽  
Odile Gayet ◽  
Véronique Gigoux ◽  
Pierre Cordelier ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Thyroid Hormone ◽  
Ubiquitin Ligase ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
E3 Ubiquitin Ligase ◽  
Proteasomal Degradation ◽  
Interacting Protein

Abstract 1212: Mutant p53 stabilizes and protects the transcription factor ETS2 from proteasomal degradation by the ubiquitin ligase COP1/DET1

2015 ◽  
Author(s):  
Zunamys I. Carrero ◽  
Madhusudhan Kollareddy ◽  
Krishna M. Chauhan ◽  
Gopalakrishnan Ramakrishnan ◽  
Luis A. Martinez
Keyword(s):  
Transcription Factor ◽  
Ubiquitin Ligase ◽  
Proteasomal Degradation ◽  
Mutant P53

scholarly journals The Transcription Factor Atf1 Binds and Activates the APC/C Ubiquitin Ligase in Fission Yeast

2009 ◽  
Vol 284 (36) ◽  
pp. 23989-23994 ◽  
Author(s):  
Aslihan Ors ◽  
Margaret Grimaldi ◽  
Yuu Kimata ◽  
Caroline R. M. Wilkinson ◽  
Nic Jones ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fission Yeast ◽  
Ubiquitin Ligase

scholarly journals Autographa californica Nucleopolyhedrovirus AC141 (Exon0), a Potential E3 Ubiquitin Ligase, Interacts with Viral Ubiquitin and AC66 To Facilitate Nucleocapsid Egress

2017 ◽  
Vol 92 (3) ◽  
Author(s):  
Siddhartha Biswas ◽  
Leslie G. Willis ◽  
Minggang Fang ◽  
Yingchao Nie ◽  
David A. Theilmann
Keyword(s):  
Ubiquitin Ligase ◽  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Nuclear Periphery ◽  
E3 Ubiquitin Ligase ◽  
Autographa Californica ◽  
Nucleocapsid Proteins ◽  
Systemic Spread ◽  
Autographa Californica Nucleopolyhedrovirus ◽  
Budded Virus

ABSTRACTDuring the infection cycle of Autographa californica multiple nucleopolyhedrovirus (AcMNPV), two forms of virions are produced, budded virus (BV) and occlusion-derived virus (ODV). Nucleocapsids that form BV have to egress from the nucleus, whereas nucleocapsids that form ODV remain inside the nucleus. The molecular mechanism that determines whether nucleocapsids remain inside or egress from the nucleus is unknown. AC141 (a predicted E3 ubiquitin ligase) and viral ubiquitin (vUbi) have both been shown to be required for efficient BV production. In this study, it was hypothesized that vUbi interacts with AC141, and in addition, that this interaction was required for BV production. Deletion of bothac141andvubirestricted viral infection to a single cell, and BV production was completely eliminated. AC141 was ubiquitinated by either vUbi or cellular Ubi, and this interaction was required for optimal BV production. Nucleocapsids in BV, but not ODV, were shown to be specifically ubiquitinated by vUbi, including a 100-kDa protein, as well as high-molecular-weight conjugates. The viral ubiquitinated 100-kDa BV-specific nucleocapsid protein was identified as AC66, which is known to be required for BV production and was shown by coimmunoprecipitation and mass spectrometry to interact with AC141. Confocal microscopy also showed that AC141, AC66, and vUbi interact at the nuclear periphery. These results suggest that ubiquitination of nucleocapsid proteins by vUbi functions as a signal to determine if a nucleocapsid will egress from the nucleus and form BV or remain in the nucleus to form ODV.IMPORTANCEBaculoviruses produce two types of virions called occlusion-derived virus (ODV) and budded virus (BV). ODVs are required for oral infection, whereas BV enables the systemic spread of virus to all host tissues, which is critical for killing insects. One of the important steps for BV production is the export of nucleocapsids out of the nucleus. This study investigated the molecular mechanisms that enable the selection of nucleocapsids for nuclear export instead of being retained within the nucleus, where they would become ODV. Our data show that ubiquitination, a universal cellular process, specifically tags nucleocapsids of BV, but not those found in ODV, using a virus-encoded ubiquitin (vUbi). Therefore, ubiquitination may be the molecular signal that determines if a nucleocapsid is destined to form a BV, thus ensuring lethal infection of the host.

Abstract 085: CHIP: E3 Ubiquitin Ligase Mediates Proteasomal Degradation of Neuronal Nitric Oxide Synthase in the Paraventricular Nucleus of Rats with Heart Failure

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Neeru M Sharma ◽  
Kenichi Katsurada ◽  
Xuefei Liu ◽  
Kaushik P Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Paraventricular Nucleus ◽  
Ubiquitin Ligase ◽  
Protein A ◽  
Neuronal Nitric Oxide Synthase ◽  
Proteasomal Degradation ◽  
Oxide Synthase

The exaggerated sympathetic drive is a characteristic of heart failure (HF) due to reduced neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus (PVN). Previously we have shown that there were increased accumulation of nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of rats with HF (1.0±0.05 Sham vs. 1.29±0.06 HF) due to the increased levels of PIN (a protein inhibitor of nNOS, known to dissociate nNOS dimers into monomers) (0.76±0.10 Sham vs. 1.12±0.09 HF) and decreased levels of tetrahydrobiopterin (BH4): a cofactor required for stabilization of nNOS dimers (0.62±0.02 Sham vs. 0.44±0.03 HF). We also showed that there is blunted nitric oxide-mediated inhibition of sympathetic tone via the PVN in HF. Here we examined whether CHIP(C-terminus of Hsp70 -interacting protein), a chaperone-dependent E3 ubiquitin-protein isopeptide ligase known to ubiquitylate Hsp90-chaperoned proteins could act as an ubiquitin ligase for nNOS in the PVN. Immunofluorescence studies revealed colocalization of nNOS and CHIP in the PVN indicating their possible interaction. CHIP expression was increased by 50% in the PVN of rats with HF(0.96±0.08 Sham vs.1.44±0.10* HF). It is shown that Hsp90 protects nNOS from ubiquitination while Hsp70 promotes the ubiquitination and degradation. We observed significant upregulation of Hsp70 (0.49±0.03 Sham vs. 0.65±0.02* HF) with a trend toward the decrease in Hsp90 expression (0.90±0.07 Sham vs. 0.71±0.06 HF). The opposing effects of the two chaperones could account for the increased CHIP-mediated ubiquitination and degradation of dysfunctional nNOS monomers in the PVN of rats with HF. Furthermore, neuronal NG108-15 cell line transfected with the pCMV3-CHIP-GFP spark (CHIP overexpression plasmid) showed approximately 74% increase in CHIP with concomitant 49% decrease in nNOS expression. In vitro ubiquitination assay in NG108 cells transfected with pCMV-(HA-Ub) 8 and pCMV3-CHIP-GFP spark plasmid reveal increased HA-Ub-nNOS conjugates (1.13 ± 0.09 Scramble vs. 1.65 ± 0.12* CHIP plasmid). Taken together, our results identify CHIP as an E3 ligase for ubiquitination of dysfunctional nNOS and CHIP expression is augmented during HF leading to increased proteasomal degradation of nNOS in the PVN.

The ubiquitin specific protease USP34 protects the ubiquitin ligase gp78 from proteasomal degradation

2019 ◽  
Vol 509 (2) ◽  
pp. 348-353 ◽  
Author(s):  
Hui Wang ◽  
Donghong Ju ◽  
Dhong-Hyo Kho ◽  
Huanjie Yang ◽  
Li Li ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Proteasomal Degradation ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

E3 ubiquitin ligase HECW2 mediates the proteasomal degradation of HP1 isoforms

2018 ◽  
Vol 503 (4) ◽  
pp. 2478-2484 ◽  
Author(s):  
Vidhya Krishnamoorthy ◽  
Richa Khanna ◽  
Veena K. Parnaik
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Proteasomal Degradation
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