LIVIVO - Search results -

Search results

Result 1 - 10 of total 60

Search options

Article ; Online: Editorial overview: Hot targets and new modalities.

Ciulli, Alessio / Wertz, Ingrid E

2021 Volume 62, Page(s) A1–A3

MeSH term(s)	Antineoplastic Agents/metabolism ; Carrier Proteins/metabolism ; Cytokines/metabolism ; Humans ; Immunotherapy ; Neoplasms/metabolism ; Neoplasms/therapy ; Receptor Protein-Tyrosine Kinases/metabolism ; Sialic Acid Binding Immunoglobulin-like Lectins/metabolism ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents ; Carrier Proteins ; Cytokines ; Sialic Acid Binding Immunoglobulin-like Lectins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2021-06-08
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2021.04.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4986: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Exploiting the Cullin E3 Ligase Adaptor Protein SKP1 for Targeted Protein Degradation.

Hong, Seong Ho / Divakaran, Anand / Osa, Akane / Huang, Oscar W / Wertz, Ingrid E / Nomura, Daniel K

ACS chemical biology

2024 Volume 19, Issue 2, Page(s) 442–450

Abstract: Targeted protein degradation with proteolysis targeting chimeras (PROTACs) is a powerful therapeutic modality for eliminating disease-causing proteins through targeted ubiquitination and proteasome-mediated degradation. Most PROTACs have exploited ... ...

Abstract	Targeted protein degradation with proteolysis targeting chimeras (PROTACs) is a powerful therapeutic modality for eliminating disease-causing proteins through targeted ubiquitination and proteasome-mediated degradation. Most PROTACs have exploited substrate receptors of Cullin-RING E3 ubiquitin ligases such as cereblon and VHL. Whether core, shared, and essential components of the Cullin-RING E3 ubiquitin ligase complex can be used for PROTAC applications remains less explored. Here, we discovered a cysteine-reactive covalent recruiter EN884 against the SKP1 adapter protein of the SKP1-CUL1-F-box containing the SCF complex. We further showed that this recruiter can be used in PROTAC applications to degrade neo-substrate proteins such as BRD4 and the androgen receptor in a SKP1- and proteasome-dependent manner. Our studies demonstrate that core and essential adapter proteins within the Cullin-RING E3 ubiquitin ligase complex can be exploited for targeted protein degradation applications and that covalent chemoproteomic strategies can enable recruiter discovery against these targets.
MeSH term(s)	Ubiquitin-Protein Ligases/metabolism ; Cullin Proteins/metabolism ; Proteolysis ; Proteasome Endopeptidase Complex/metabolism ; Nuclear Proteins/metabolism ; Transcription Factors/metabolism ; S-Phase Kinase-Associated Proteins/metabolism ; Adaptor Proteins, Signal Transducing/metabolism
Chemical Substances	Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Cullin Proteins ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Nuclear Proteins ; Transcription Factors ; S-Phase Kinase-Associated Proteins ; Adaptor Proteins, Signal Transducing
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.3c00642
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Exploiting the Cullin E3 Ligase Adaptor Protein SKP1 for Targeted Protein Degradation.

Hong, Seong Ho / Osa, Akane / Huang, Oscar W / Wertz, Ingrid E / Nomura, Daniel K

bioRxiv : the preprint server for biology

2023

Abstract: Targeted protein degradation with Proteolysis Targeting Chimeras (PROTACs) is a powerful therapeutic modality for eliminating disease-causing proteins through targeted ubiquitination and proteasome-mediated degradation. Most PROTACs have exploited ... ...

Abstract	Targeted protein degradation with Proteolysis Targeting Chimeras (PROTACs) is a powerful therapeutic modality for eliminating disease-causing proteins through targeted ubiquitination and proteasome-mediated degradation. Most PROTACs have exploited substrate receptors of Cullin-RING E3 ubiquitin ligases such as cereblon and VHL. Whether core, shared, and essential components of the Cullin-RING E3 ubiquitin ligase complex can be used for PROTAC applications remains less explored. Here, we discovered a cysteine-reactive covalent recruiter EN884 against the SKP1 adapter protein of the SKP1-CUL1-F-box containing SCF complex. We further showed that this recruiter can be used in PROTAC applications to degrade neo-substrate proteins such as BRD4 and the androgen receptor in a SKP1- and proteasome-dependent manner. Our studies demonstrate that core and essential adapter proteins within the Cullin-RING E3 ubiquitin ligase complex can be exploited for targeted protein degradation applications and that covalent chemoproteomic strategies can enable recruiter discovery against these targets.
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.20.563371
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Structurally-defined deubiquitinase inhibitors provide opportunities to investigate disease mechanisms.

Wertz, Ingrid E / Murray, Jeremy M

Drug discovery today. Technologies

2019 Volume 31, Page(s) 109–123

Abstract: The Ubiquitin/Proteasome System comprises an essential cellular mechanism for regulated protein degradation. Ubiquitination may also promote the assembly of protein complexes that initiate intracellular signaling cascades. Thus, proper regulation of ... ...

Abstract	The Ubiquitin/Proteasome System comprises an essential cellular mechanism for regulated protein degradation. Ubiquitination may also promote the assembly of protein complexes that initiate intracellular signaling cascades. Thus, proper regulation of substrate protein ubiquitination is essential for maintaining normal cellular physiology. Deubiquitinases are the class of enzymes responsible for removing ubiquitin modifications from target proteins and have been implicated in regulating human disease. As such, deubiquitinases are now recognized as emerging drug targets. Small molecule deubiquitinase inhibitors have been developed; among those, inhibitors for the deubiquitinases USP7 and USP14 are the best-characterized given that they are structurally validated. In this review we discuss the normal physiological roles of the USP7 and USP14 deubiquitinases as well as the pathological conditions associated with their dysfunction, with a focus on oncology and neurodegenerative diseases. We also review structural biology of USP7 and USP14 enzymes and the characterization of their respective inhibitors, highlighting the various molecular mechanisms by which these deubiquitinases may be functionally inhibited. Finally, we summarize the cellular and in vivo studies performed using the structurally-validated USP7 and USP14 inhibitors.
MeSH term(s)	Animals ; Humans ; Molecular Structure ; Pyrroles/chemistry ; Pyrroles/pharmacology ; Ubiquitin Thiolesterase/antagonists & inhibitors ; Ubiquitin Thiolesterase/chemistry ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Pyrroles ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2019-04-01
Publishing country	England
Document type	Journal Article ; Review
ISSN	1740-6749
ISSN (online)	1740-6749
DOI	10.1016/j.ddtec.2019.02.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: TNFR1-activated NF-κB signal transduction: regulation by the ubiquitin/proteasome system.

Wertz, Ingrid E

Current opinion in chemical biology

2014 Volume 23, Page(s) 71–77

Abstract: The Tumor Necrosis Factor Receptor-1 (TNFR1) is a central regulator of inflammation, cell death, and cellular proliferation. As such, alterations in TNFR1 signaling are associated with numerous diseases ranging from autoimmune syndromes to cancer. ... ...

Abstract	The Tumor Necrosis Factor Receptor-1 (TNFR1) is a central regulator of inflammation, cell death, and cellular proliferation. As such, alterations in TNFR1 signaling are associated with numerous diseases ranging from autoimmune syndromes to cancer. Understanding the regulation of TNFR1 signaling is therefore of considerable importance. The transduction of signaling events in the TNFR1 pathway--from ligand binding through transcriptional regulation--is regulated at nearly every step by post-translational modifications, including ubiquitination. In this review both endogenous and pharmacologic inhibitors of TNFR1 signaling, and how these impact the ubiquitin system, will be discussed.
MeSH term(s)	Animals ; Humans ; NF-kappa B/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; Signal Transduction ; Ubiquitin/metabolism
Chemical Substances	NF-kappa B ; Receptors, Tumor Necrosis Factor, Type I ; Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2014.10.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4986: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: From Discovery to Bedside: Targeting the Ubiquitin System.

Wertz, Ingrid E / Wang, Xiaojing

Cell chemical biology

2018 Volume 26, Issue 2, Page(s) 156–177

Abstract: The ubiquitin/proteasome system is a primary conduit for selective intracellular protein degradation. Since its discovery over 30 years ago, this highly regulated system continues to be an active research area for drug discovery that is exemplified by ... ...

Abstract	The ubiquitin/proteasome system is a primary conduit for selective intracellular protein degradation. Since its discovery over 30 years ago, this highly regulated system continues to be an active research area for drug discovery that is exemplified by several approved drugs. Here we review compounds in preclinical testing, clinical trials, and approved drugs, with the aim of highlighting innovative discoveries and breakthrough therapies that target the ubiquitin system.
MeSH term(s)	Drug Evaluation, Preclinical ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/metabolism ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors ; Proto-Oncogene Proteins c-mdm2/metabolism ; Ubiquitin/chemistry ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/chemistry ; Ubiquitin-Activating Enzymes/metabolism ; Ubiquitin-Conjugating Enzymes/chemistry ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
Chemical Substances	Enzyme Inhibitors ; Ubiquitin ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Ubiquitin-Activating Enzymes (EC 6.2.1.45)
Language	English
Publishing date	2018-12-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2018.10.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Covalent Degrader of the Oncogenic Transcription Factor β-Catenin.

Gowans, Flor A / Forte, Nafsika / Hatcher, Justin / Huang, Oscar W / Wang, Yangzhi / Poblano, Belen E Altamirano / Wertz, Ingrid E / Nomura, Daniel K

bioRxiv : the preprint server for biology

2023

Abstract: β-catenin (CTNNB1) is an oncogenic transcription factor that is important in cell-cell adhesion and transcription of cell proliferation and survival genes that drives the pathogenesis of many different types of cancers. However, direct pharmacological ... ...

Abstract	β-catenin (CTNNB1) is an oncogenic transcription factor that is important in cell-cell adhesion and transcription of cell proliferation and survival genes that drives the pathogenesis of many different types of cancers. However, direct pharmacological targeting of CTNNB1 has remained challenging deeming this transcription factor as "undruggable." Here, we have performed a screen with a library of cysteine-reactive covalent ligands to identify a monovalent degrader EN83 that depletes CTNNB1 in a ubiquitin-proteasome-dependent manner. We show that EN83 directly and covalently targets CTNNB1 through targeting four distinct cysteines within the armadillo repeat domain-C439, C466, C520, and C619-leading to a destabilization of CTNNB1. Using covalent chemoproteomic approaches, we show that EN83 directly engages CTNNB1 in cells with a moderate degree of selectivity. We further demonstrate that direct covalent targeting of three of these four cysteines--C466, C520, and C619--in cells contributes to CTNNB1 degradation in cells. We also demonstrate that EN83 can be further optimized to yield more potent CTNNB1 binders and degraders. Our results show that chemoproteomic approaches can be used to covalently target and degrade challenging transcription factors like CTNNB1 through a destabilization-mediated degradation.
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.31.565018
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Allosteric Inhibitors of the SARS-COV-2 Papain-like Protease Domain Induce Proteasomal Degradation of Its Parent Protein NSP3.

Cockram, Peter E / Walters, Benjamin T / Lictao, Aaron / Shanahan, Frances / Wertz, Ingrid E / Foster, Scott A / Rudolph, Joachim

ACS chemical biology

2023 Volume 19, Issue 1, Page(s) 22–36

Abstract: The papain-like protease of SARS-COV-2 is essential for viral replication and pathogenesis. Its location within a much larger multifunctional protein, NSP3, makes it an ideal candidate for a targeted degradation approach capable of eliminating multiple ... ...

Abstract	The papain-like protease of SARS-COV-2 is essential for viral replication and pathogenesis. Its location within a much larger multifunctional protein, NSP3, makes it an ideal candidate for a targeted degradation approach capable of eliminating multiple functions with a single-molecule treatment. In this work, we have developed a HiBiT-based cellular model to study NSP3 degradation and used this platform for the discovery of monovalent NSP3 degraders. We present previously unreported degradation activity of published papain-like protease inhibitors. Follow-up exploration of structure-activity relationships and mechanism-of-action studies points to the recruitment of the ubiquitin-proteasome machinery that is solely driven by site occupancy, regardless of molecular features of the ligand. Supported by HDX data, we hypothesize that binding-induced structural changes in NSP3 trigger the recruitment of an E3 ligase and lead to proteasomal degradation.
MeSH term(s)	Humans ; Papain/metabolism ; Viral Nonstructural Proteins/metabolism ; SARS-CoV-2/chemistry ; COVID-19 ; Protease Inhibitors/metabolism ; Coronavirus Papain-Like Proteases
Chemical Substances	Papain (EC 3.4.22.2) ; papain-like protease, SARS-CoV-2 (EC 3.4.22.2) ; Viral Nonstructural Proteins ; Protease Inhibitors ; Coronavirus Papain-Like Proteases (EC 3.4.22.2)
Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.3c00312
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Length Matters: MINDY Is a New Deubiquitinase Family that Preferentially Cleaves Long Polyubiquitin Chains.

Maurer, Till / Wertz, Ingrid E

Molecular cell

2016 Volume 63, Issue 1, Page(s) 4–6

Abstract: Abdul Rehman and colleagues identify a sixth family of deubiquitinase enzymes that are highly conserved throughout eukaryotes and show a remarkable selectivity for cleaving extended Lys-48-linked polyubiquitin chains. ...

Abstract	Abdul Rehman and colleagues identify a sixth family of deubiquitinase enzymes that are highly conserved throughout eukaryotes and show a remarkable selectivity for cleaving extended Lys-48-linked polyubiquitin chains.
MeSH term(s)	Deubiquitinating Enzymes ; Eukaryota ; Humans ; Polyubiquitin
Chemical Substances	Polyubiquitin (120904-94-1) ; Deubiquitinating Enzymes (EC 3.4.19.12)
Language	English
Publishing date	2016-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2016.06.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5055: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Ubiquitination in the regulation of inflammatory cell death and cancer.

Cockram, Peter E / Kist, Matthias / Prakash, Sumit / Chen, Si-Han / Wertz, Ingrid E / Vucic, Domagoj

Cell death and differentiation

2021 Volume 28, Issue 2, Page(s) 591–605

Abstract: The ubiquitin system is complex, multifaceted, and is crucial for the modulation of a vast number of cellular processes. Ubiquitination is tightly regulated at different levels by a range of enzymes including E1s, E2s, and E3s, and an array of DUBs. The ... ...

Abstract	The ubiquitin system is complex, multifaceted, and is crucial for the modulation of a vast number of cellular processes. Ubiquitination is tightly regulated at different levels by a range of enzymes including E1s, E2s, and E3s, and an array of DUBs. The UPS directs protein degradation through the proteasome, and regulates a wide array of cellular processes including transcription and epigenetic factors as well as key oncoproteins. Ubiquitination is key to the dynamic regulation of programmed cell death. Notably, the TNF signaling pathway is controlled by competing ubiquitin conjugation and deubiquitination, which governs both proteasomal degradation and signaling complex formation. In the inflammatory response, ubiquitination is capable of both activating and dampening inflammasome activation through the control of either protein stability, complex formation, or, in some cases, directly affecting receptor activity. In this review, we discuss the enzymes and targets in the ubiquitin system that regulate fundamental cellular processes regulating cell death, and inflammation, as well as disease consequences resulting from their dysregulation. Finally, we highlight several pre-clinical and clinical compounds that regulate ubiquitin system enzymes, with the aim of restoring homeostasis and ameliorating diseases.
MeSH term(s)	Animals ; Apoptosis ; Humans ; Inflammation/metabolism ; Neoplasms/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Signal Transduction ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
Chemical Substances	Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-01-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-020-00708-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 80: Show issues

Order via subito

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito