Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EIF3H is presumed to be a critical translational initiation factor. Here, our unbiased screening for tumor invasion factors has identified an unexpected role for EIF3H as a deubiquitylating enzyme that dictates breast tumor invasion and metastasis by modulating the Hippo-YAP pathway. EIF3H catalyzed YAP for deubiquitylation, resulting in its stabilization. Structure-based molecular modeling and simulations coupled with biochemical characterization unveiled a unique catalytic mechanism for EIF3H in dissociating polyubiquitin chains from YAP through a catalytic triad consisting of Asp90, Asp91, and Gln121. Trp119 and Tyr 140 on EIF3H directly interacted with the N-terminal region of YAP1, facilitating complex formation of EIF3H and YAP1 for YAP1 deubiquitylation. Stabilization of YAP via elevated EIF3H promoted tumor invasion and metastasis. Interference of EIF3H-mediated YAP deubiquitylation blocked YAP-induced tumor progression and metastasis in breast cancer models. These findings point to a critical role for YAP regulation by EIF3H in tumor invasion and metastasis. SIGNIFICANCE: This work demonstrates that EIF3H is a novel bona fide deubiquitinase that counteracts YAP ubiquitylation and proteolysis, and stabilization of YAP by EIF3H promotes tumor invasion and metastasis.
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PMID:EIF3H Orchestrates Hippo Pathway-Mediated Oncogenesis via Catalytic Control of YAP Stability. 3226 44

To increase coverage of protein identification of an Agaricus bisporus fruiting body, we analyzed the crude protein fraction of the fruiting body by using a shotgun proteomics approach where 7 MudPIT (Multi-Protein identification Technology) runs were conducted and the MS/MS spectra from the 7 MudPIT runs were merged. Overall, 3093 non-redundant proteins were identified to support the expression of those genes annotated in the genome database of Agaricus bisporus. The physicochemical properties of the identified proteins, i.e., wide pI value range and molecular mass range, were indicative of unbiased protein identification. The relative quantification of the identified proteins revealed that K5XI50 (Aldedh domain-containing protein) and K5XEW1 (Ubiquitin-like domain-containing protein) were highly abundant in the fruiting body. Based on the information in the Uniprot (Universal Protein Resource) database for A. bisporus, only approximately 53% of the 3093 identified proteins have been functionally described and approximately 47% of the proteins remain uncharacterized. Gene Ontology analysis revealed that the majority of proteins were annotated with a biological process, and proteins associated with coiled-coil (12.8%) and nucleotide binding (8.21%) categories were dominant. The Kyoto Encyclopedia of Genes and Genome analysis revealed that proteins involved in biosynthesis of secondary metabolites and tyrosine metabolism were enriched in a fruiting body of Agaricus bisporus, suggesting that the proteins are associated with antioxidant metabolites.
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PMID:Increasing Coverage of Proteome Identification of the Fruiting Body of Agaricus bisporus by Shotgun Proteomics. 3242 98

Type I interferons are broadly used for antiviral therapy in clinical. However, the IFNs-mediated antiviral efficacy is commonly restricted by negative regulators. Here, we show that the ubiquitin-specific protease 5 (USP5) inhibits the IFNs-induced p-STAT1 activation (phosphorylation at tyrosine site of STAT1) and its downstream antiviral genes expression. We clarify that USP5 physically interacts with SMURF1 (Smad ubiquitination regulating factor 1) and IFNs signaling regulates the interaction and turnover of both proteins. USP5 enhances the stability and turnover of SMURF1 via decreasing its polyubiquitin expression level, which caused STAT1 to decrease. Importantly, USP5 is also involved in the SMURF1-mediated antiviral response, and its small-molecule inhibitor PYR41 remarkably enhances the IFNs antiviral efficacy. These findings reveal a previously unrecognized function of the USP5 and USP5-SMURF1 axis in regulating the IFNs-mediated antiviral activity.
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PMID:Ubiquitin specific protease 5 negatively regulates the IFNs-mediated antiviral activity via targeting SMURF1. 3268 98


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