Activity‐based probes for the ubiquitin conjugation–deconjugation machinery: new chemistries, new tools, and new insights DOI Open Access
David S. Hewings,

John A. Flygare,

Matthew Bogyo

et al.

FEBS Journal, Journal Year: 2017, Volume and Issue: 284(10), P. 1555 - 1576

Published: Feb. 14, 2017

The reversible post-translational modification of proteins by ubiquitin and ubiquitin-like regulates almost all cellular processes, affecting protein degradation, localization, complex formation. Deubiquitinases (DUBs) are proteases that remove modifications or cleave chains. Most DUBs cysteine proteases, which makes them well suited for study activity-based probes. These DUB probes report on deubiquitinase activity reacting covalently with the active site in an enzyme-catalyzed manner. They have proven to be important tools selectivity proteolytic different settings, identify novel DUBs, characterize inhibitors. Inspired efficacy several groups recently reported conjugation machinery (E1, E2, E3 enzymes). Many these enzymes, while not also posses residues can targeted covalent In this review, we will discuss how features probe (cysteine-reactive group, recognition element, reporter tag) affect reactivity suitability certain experimental applications. We review diverse applications current probes, need new types emerging aspects biology.

Language: Английский

NF-κB signaling in inflammation DOI Creative Commons
Ting Liu, Lingyun Zhang,

Donghyun Joo

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2017, Volume and Issue: 2(1)

Published: July 14, 2017

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions serves as a pivotal mediator inflammatory responses. induces the expression various pro-inflammatory genes, including those encoding cytokines chemokines, also participates in inflammasome regulation. In addition, plays critical role regulating survival, activation differentiation cells T cells. Consequently, deregulated contributes to pathogenic processes diseases. this review, we will discuss function association with diseases highlight development therapeutic strategies based on inhibition.

Language: Английский

Citations

6348
The non-canonical NF-κB pathway in immunity and inflammation DOI
Shao‐Cong Sun

Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 17(9), P. 545 - 558

Published: June 5, 2017

Language: Английский

Citations

1440
Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study DOI Creative Commons
Hui Yu, Liangbin Lin, Zhiqiang Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Sept. 21, 2020

Abstract NF-κB pathway consists of canonical and non-canonical pathways. The is activated by various stimuli, transducing a quick but transient transcriptional activity, to regulate the expression proinflammatory genes also serve as critical mediator for inflammatory response. Meanwhile, activation occurs through handful TNF receptor superfamily members. Since this involves protein synthesis, kinetics slow persistent, in concordance with its biological functions development immune cell lymphoid organ, homeostasis tightly controlled, highlighting vital roles ubiquitination these Emerging studies indicate that dysregulated activity causes inflammation-related diseases well cancers, has been long proposed potential target therapy diseases. This review attempts summarize our current knowledge updates on mechanisms regulation therapeutic application inhibition signaling cancer

Language: Английский

Citations

1320
Deubiquitylating enzymes and drug discovery: emerging opportunities DOI Open Access
Jeanine A. Harrigan,

Xavier Jacq,

Niall M.B. Martin

et al.

Nature Reviews Drug Discovery, Journal Year: 2017, Volume and Issue: 17(1), P. 57 - 78

Published: Sept. 29, 2017

Language: Английский

Citations

731
Limiting inflammation—the negative regulation of NF-κB and the NLRP3 inflammasome DOI
Inna S. Afonina, Zhenyu Zhong, Michael Karin

et al.

Nature Immunology, Journal Year: 2017, Volume and Issue: 18(8), P. 861 - 869

Published: July 19, 2017

Language: Английский

Citations

666
Mechanisms and treatment of organ failure in sepsis DOI
Christophe Lelubre, Jean‐Louis Vincent

Nature Reviews Nephrology, Journal Year: 2018, Volume and Issue: 14(7), P. 417 - 427

Published: April 24, 2018

Language: Английский

Citations

617
Regulatory mechanisms in T cell receptor signalling DOI
Guillaume Gaud, Renaud Lesourne, Paul E. Love

et al.

Nature reviews. Immunology, Journal Year: 2018, Volume and Issue: 18(8), P. 485 - 497

Published: May 22, 2018

Language: Английский

Citations

443
Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development DOI Creative Commons

Jeong-Ryul Hwang,

Yeongseon Byeon,

Donghwan Kim

et al.

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(5), P. 750 - 761

Published: May 1, 2020

Abstract T cell activation requires extracellular stimulatory signals that are mainly mediated by receptor (TCR) complexes. The TCR recognizes antigens on major histocompatibility complex molecules with the cooperation of CD4 or CD8 coreceptors. After recognition, TCR-induced signaling cascades propagate via various and second messengers induced. Consequently, many features cell-mediated immune responses determined these intracellular cascades. Furthermore, differences in magnitude direct cells toward distinct effector linages. Therefore, stringent regulation is crucial for homeostasis proper responses. Dysregulation can result anergy autoimmunity. In this review, we summarize current knowledge pathways govern how transmits into roles involved pathways.

Language: Английский

Citations

332
T cell receptor (TCR) signaling in health and disease DOI Creative Commons
Kinjal Shah, Amr Al‐Haidari, Jianmin Sun

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Dec. 13, 2021

Interaction of the T cell receptor (TCR) with an MHC-antigenic peptide complex results in changes at molecular and cellular levels cells. The outside environmental cues are translated into various signal transduction pathways within cell, which mediate activation genes help specific transcription factors. These signaling networks propagate effector enzymes, such as kinases, phosphatases, phospholipases. Integration these disparate is done adaptor proteins that non-enzymatic function serve a scaffold for protein-protein interactions. This process aids connecting proximal to distal pathways, thereby contributing full review provides comprehensive snapshot molecules involved regulating signaling, covering both enzymes adaptors, will discuss their role human disease.

Language: Английский

Citations

324
Ubiquitination in the regulation of inflammatory cell death and cancer DOI Creative Commons
Peter E. Cockram,

Matthias Kist,

Sumit Prakash

et al.

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(2), P. 591 - 605

Published: Jan. 11, 2021

The ubiquitin system is complex, multifaceted, and crucial for the modulation of a vast number cellular processes. Ubiquitination tightly regulated at different levels by range enzymes including E1s, E2s, E3s, an array DUBs. UPS directs protein degradation through proteasome, regulates wide processes transcription epigenetic factors as well key oncoproteins. to dynamic regulation programmed cell death. Notably, TNF signaling pathway controlled competing conjugation deubiquitination, which governs both proteasomal complex formation. In inflammatory response, ubiquitination capable activating dampening inflammasome activation control either stability, formation, or, in some cases, directly affecting receptor activity. this review, we discuss targets that regulate fundamental regulating death, inflammation, disease consequences resulting from their dysregulation. Finally, highlight several pre-clinical clinical compounds enzymes, with aim restoring homeostasis ameliorating diseases.

Language: Английский

Citations

319