Neuropathy Target Esterase Is Degraded by the Ubiquitin–Proteasome Pathway with ARA54 as the Ubiquitin Ligase

Biochemistry ◽  
2015 ◽  
Vol 54 (50) ◽  
pp. 7385-7392 ◽  
Author(s):  
Ding-Xin Long ◽  
Pan Wang ◽  
Ying-Jian Sun ◽  
Rui Chen ◽  
Yi-Jun Wu
Keyword(s):  
Ubiquitin Ligase ◽  
Neuropathy Target Esterase ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-Trisphosphate Receptor Ubiquitination and Degradation

2011 ◽  
Vol 286 (27) ◽  
pp. 24426-24433 ◽  
Author(s):  
Justine P. Lu ◽  
Yuan Wang ◽  
Danielle A. Sliter ◽  
Margaret M. P. Pearce ◽  
Richard J. H. Wojcikiewicz
Keyword(s):  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Endoplasmic Reticulum Membrane ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Ligase Activity ◽  
Inositol 1,4,5 Trisphosphate ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Membrane Spanning ◽  
Trisphosphate Receptor

Inositol 1,4,5-trisphosphate (IP3) receptors are endoplasmic reticulum membrane calcium channels that, upon activation, are degraded via the ubiquitin-proteasome pathway. While searching for novel mediators of IP3 receptor processing, we discovered that RNF170, an uncharacterized RING domain-containing protein, associates rapidly with activated IP3 receptors. RNF170 is predicted to have three membrane-spanning helices, is localized to the ER membrane, and possesses ubiquitin ligase activity. Depletion of endogenous RNF170 by RNA interference inhibited stimulus-induced IP3 receptor ubiquitination, and degradation and overexpression of a catalytically inactive RNF170 mutant suppressed stimulus-induced IP3 receptor processing. A substantial proportion of RNF170 is constitutively associated with the erlin1/2 (SPFH1/2) complex, which has been shown previously to bind to IP3 receptors immediately after their activation. Depletion of RNF170 did not affect the binding of the erlin1/2 complex to stimulated IP3 receptors, whereas erlin1/2 complex depletion inhibited RNF170 binding. These results suggest a model in which the erlin1/2 complex recruits RNF170 to activated IP3 receptors where it mediates IP3 receptor ubiquitination. Thus, RNF170 plays an essential role in IP3 receptor processing via the ubiquitin-proteasome pathway.

scholarly journals The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation

Science ◽  
2020 ◽  
pp. eabc9359
Author(s):  
Charlie Y. Shi ◽  
Elena R. Kingston ◽  
Benjamin Kleaveland ◽  
Daniel H. Lin ◽  
Michael W. Stubna ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Mechanistic Model ◽  
E3 Ubiquitin Ligase ◽  
Gene Repression ◽  
Loss Of Function ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Mirna Degradation ◽  
Ring E3

MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread post-transcriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive pairing to some unusual target RNAs can trigger miRNA degradation. Here we found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings suggested and supported a mechanistic model of TDMD in which target-directed proteolysis of AGO by the ubiquitin–proteasome pathway exposes the miRNA for degradation. Moreover, loss-of-function studies indicated that the ZSWIM8 Cullin-RING ligase accelerates degradation of numerous miRNAs in cells of mammals, flies, and nematodes, thereby specifying the half-lives of most short-lived miRNAs. These results elucidate the mechanism of TDMD and expand its inferred role in shaping miRNA levels in bilaterian animals.

scholarly journals The Mdm2 Ubiquitin Ligase Enhances Transcriptional Activity of Human Papillomavirus E2

2008 ◽  
Vol 83 (3) ◽  
pp. 1538-1543 ◽  
Author(s):  
Noor Gammoh ◽  
Daniela Gardiol ◽  
Paola Massimi ◽  
Lawrence Banks
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Ubiquitin Ligase ◽  
Transcriptional Activity ◽  
Critical Feature ◽  
Promoter Sequences ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Cooperative Activity

ABSTRACT The regulation of human papillomavirus (HPV) gene expression by the E2 protein is a critical feature of the viral life cycle. Previous studies have shown an important role in transcription for the ubiquitin-proteasome pathway, but its role in HPV gene expression has not been addressed. We now show that HPV E2 requires an active proteasome for its optimal transcriptional activator function. This involves an interaction with the Mdm2 ubiquitin ligase, which together with E2 acts synergistically to activate the HPV type 16 promoter. We also show that HPV E2 recruits Mdm2 onto HPV promoter sequences, providing an explanation for this cooperative activity.

scholarly journals Transferable Domain in the G1 Cyclin Cln2 Sufficient To Switch Degradation of Sic1 from the E3 Ubiquitin Ligase SCFCdc4 to SCFGrr1

2002 ◽  
Vol 22 (13) ◽  
pp. 4463-4476 ◽  
Author(s):  
Catherine Berset ◽  
Peter Griac ◽  
Rebecca Tempel ◽  
Janna La Rue ◽  
Curt Wittenberg ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Kinase Inhibitor ◽  
E3 Ubiquitin Ligase ◽  
Phosphorylation Sites ◽  
Dependent Manner ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
F Box Protein

ABSTRACT Degradation of Saccharomyces cerevisiae G1 cyclins Cln1 and Cln2 is mediated by the ubiquitin-proteasome pathway and involves the SCF E3 ubiquitin-ligase complex containing the F-box protein Grr1 (SCFGrr1). Here we identify the domain of Cln2 that confers instability and describe the signals in Cln2 that result in binding to Grr1 and rapid degradation. We demonstrate that mutants of Cln2 that lack a cluster of four Cdc28 consensus phosphorylation sites are highly stabilized and fail to interact with Grr1 in vivo. Since one of the phosphorylation sites lies within the Cln2 PEST motif, a sequence rich in proline, aspartate or glutamate, serine, and threonine residues found in many unstable proteins, we fused various Cln2 C-terminal domains containing combinations of the PEST and the phosphoacceptor motifs to stable reporter proteins. We show that fusion of the Cln2 domain to a stabilized form of the cyclin-dependent kinase inhibitor Sic1 (ΔN-Sic1), a substrate of SCFCdc4, results in degradation in a phosphorylation-dependent manner. Fusion of Cln2 degradation domains to ΔN-Sic1 switches degradation of Sic1 from SCFCdc4 to SCFGrr1. ΔN-Sic1 fused with a Cln2 domain containing the PEST motif and four phosphorylation sites binds to Grr1 and is unstable and ubiquitinated in vivo. Interestingly, the phosphoacceptor domain of Cln2 binds to Grr1 but is not ubiquitinated and is stable. In summary, we have identified a small transferable domain in Cln2 that can redirect a stabilized SCFCdc4 target for SCFGrr1-mediated degradation by the ubiquitin-proteasome pathway.

scholarly journals Ligand-dependent Degradation of Smad3 by a Ubiquitin Ligase Complex of ROC1 and Associated Proteins

2001 ◽  
Vol 12 (5) ◽  
pp. 1431-1443 ◽  
Author(s):  
Minoru Fukuchi ◽  
Takeshi Imamura ◽  
Tomoki Chiba ◽  
Takanori Ebisawa ◽  
Masahiro Kawabata ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Ring Finger ◽  
Transforming Growth Factor Β ◽  
Dependent Manner ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Smads are signal mediators for the members of the transforming growth factor-β (TGF-β) superfamily. Upon phosphorylation by the TGF-β receptors, Smad3 translocates into the nucleus, recruits transcriptional coactivators and corepressors, and regulates transcription of target genes. Here, we show that Smad3 activated by TGF-β is degraded by the ubiquitin–proteasome pathway. Smad3 interacts with a RING finger protein, ROC1, through its C-terminal MH2 domain in a ligand-dependent manner. An E3 ubiquitin ligase complex ROC1-SCFFbw1a consisting of ROC1, Skp1, Cullin1, and Fbw1a (also termed βTrCP1) induces ubiquitination of Smad3. Recruitment of a transcriptional coactivator, p300, to nuclear Smad3 facilitates the interaction with the E3 ligase complex and triggers the degradation process of Smad3. Smad3 bound to ROC1-SCFFbw1a is then exported from the nucleus to the cytoplasm for proteasomal degradation. TGF-β/Smad3 signaling is thus irreversibly terminated by the ubiquitin–proteasome pathway.

The Ubiquitin-Proteasome Pathway an Emerging Anticancer Strategy for Therapeutics: A Patent Analysis

2015 ◽  
Vol 10 (2) ◽  
pp. 201-213 ◽  
Author(s):  
Chakresh Jain ◽  
Shivam Arora ◽  
Aparna Khanna ◽  
Money Gupta ◽  
Gulshan Wadhwa ◽  
...  
Keyword(s):  
Patent Analysis ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway
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