Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy‐related apoptosis DOI Creative Commons
Xin Zhen,

Kristian Holgersson,

Pengcheng Zhu

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(7)

Published: July 1, 2024

Glioma is a central nervous system (CNS) malignant tumor with high heterogeneity and mortality, which severely threatens the health of patients. The overall survival glioma patients relatively short it critical to identify new molecular targets for developing effective treatment strategies. UBE2K ubiquitin conjugating enzyme oncogenic function in several tumors. However, whether participates gliomas remains unknown. Herein, cells, was found highly expressed U87 U251 cells. Subsequently, cells were transfected si-UBE2K silence UBE2K, si-NC transfection as negative control. In both cell viability sharply reduced by transfecting 48 72 h. Markedly decreased colony number, number migrated invaded declined relative wound healing rate observed Moreover, Bcl-2 level markedly reduced, while Bax cleaved-caspase-3 levels increased after transfection. Furthermore, p62 signally declined, Beclin-1 LC-3 II/I greatly facilitating effect on apoptosis autophagy abolished coculture 3-MA, an inhibitor autophagy. Collectively, facilitated vitro growth possibly inhibiting autophagy-related apoptosis, might be promising target treating glioma.

Language: Английский

Assembly and function of branched ubiquitin chains DOI

SriDurgaDevi Kolla,

Mengchen Ye, Kevin G. Mark

et al.

Trends in Biochemical Sciences, Journal Year: 2022, Volume and Issue: 47(9), P. 759 - 771

Published: May 1, 2022

Language: Английский

Citations

66

The emerging roles of non-canonical ubiquitination in proteostasis and beyond DOI Creative Commons

Yoshino Akizuki,

Stephanie Kaypee, Fumiaki Ohtake

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)

Published: March 22, 2024

Ubiquitin regulates various cellular functions by posttranslationally modifying substrates with diverse ubiquitin codes. Recent discoveries of new chain topologies, types bonds, and non-protein have substantially expanded the complexity code. Here, we describe system covering basic principles recent related to mechanisms, technologies, biological importance.

Language: Английский

Citations

10

K48- and K63-linked ubiquitin chain interactome reveals branch- and length-specific ubiquitin interactors DOI Creative Commons
Anita Waltho, Oliver Popp, Christopher Lenz

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(8), P. e202402740 - e202402740

Published: May 21, 2024

The ubiquitin (Ub) code denotes the complex Ub architectures, including chains of different lengths, linkage types, and combinations, which enable ubiquitination to control a wide range protein fates. Although many linkage-specific interactors have been described, how are able decode more architectures is not fully understood. We conducted interactor screen, in humans yeast, using varying as well homotypic heterotypic branched two most abundant types-lysine 48-linked (K48) lysine 63-linked (K63) Ub. identified some first K48/K63-linked branch-specific interactors, histone ADP-ribosyltransferase PARP10/ARTD10, E3 ligase UBR4, huntingtin-interacting HIP1. Furthermore, we revealed importance chain length by identifying with preference for Ub3 over Ub2 chains, Ub-directed endoprotease DDI2, autophagy receptor CCDC50, p97 adaptor FAF1. Crucially, compared datasets collected common deubiquitinase inhibitors-chloroacetamide N-ethylmaleimide. This inhibitor-dependent highlighting inhibitor consideration during pulldown studies. dataset key resource understanding read.

Language: Английский

Citations

9

Structure of UBE2K–Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension DOI Creative Commons
Mark A. Nakasone, K.A. Majorek, Mads Gabrielsen

et al.

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(4), P. 422 - 431

Published: Jan. 13, 2022

Abstract Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub synthesis remains elusive due to transient nature handover. Here, we present structure a chemically trapped complex E2 UBE2K covalently linked donor and acceptor di-Ub, primed by RING E3. The reveals basis recognition active site residues C-terminal Ub-associated (UBA) domain, impart specificity catalysis. Furthermore, unveils multiple Ub-binding surfaces on UBA domain that allow binding modes K48- K63-linked chains. This multivalent feature serves recruit ubiquitinated overcome weak affinity thereby promote elongation. These findings elucidate processive formation UBE2K.

Language: Английский

Citations

34

Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2 DOI Creative Commons

Zhaoyuan Chen,

Jie Zhang,

Shenjia Gao

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: July 30, 2024

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The inflammatory cytokine storm causes systemic damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased sepsis-induced (ALI). activated MEK/ERK pathway and inhibited Skp2 pulmonary epithelium, resulting reduction K48 ubiquitination solute carrier family 3 member (SLC3A2), thereby impairing its membrane localization cystine/glutamate exchange function. Consequently, intracellular redox reactions induced ferroptosis epithelial cells, leading injury. Finally, demonstrated intravenous administration mRNA-encapsulating lipid nanoparticles (LNPs) epithelium alleviated septic mice. Taken together, these data provide an innovative understanding underlying mechanisms ALI promising therapeutic strategy for

Language: Английский

Citations

4

Branched ubiquitin code: from basic biology to targeted protein degradation DOI Open Access
Fumiaki Ohtake

The Journal of Biochemistry, Journal Year: 2022, Volume and Issue: 171(4), P. 361 - 366

Published: Jan. 10, 2022

Abstract Protein ubiquitylation regulates numerous pathways, and the diverse information encoded by various forms of is known as ubiquitin code. Recent studies revealed that branched chains are abundant in mammalian cells regulate important pathways. They include proteasomal degradation misfolded disease-causing proteins, regulation NF-κB signalling apoptotic cell fate decisions. Targeted protein through chemical degraders emerged a transformative therapeutic paradigm aimed at inducing disappearance unwanted cellular proteins. To further improve efficacy target expand its applications, understanding molecular mechanism degraders’ action from view code biology required. In this review, I discuss roles biological pathways chemically induced targeted focusing on codes we have characterized.

Language: Английский

Citations

19

Ubiquitin-modifying enzymes in Huntington’s disease DOI Creative Commons
Karen A. Sap, Karlijne W. Geijtenbeek, Sabine Schipper-Krom

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 8, 2023

Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion in the N-terminus of HTT gene. The translates into polyglutamine mutant (mHTT) protein, resulting intracellular aggregation and neurotoxicity. Lowering mHTT protein reducing synthesis or improving degradation would delay prevent onset HD, ubiquitin-proteasome system (UPS) could be an important pathway to clear proteins prior aggregation. UPS not impaired proteasomes can degrade entirely when targeted for degradation. However, differently ubiquitinated compared wild-type (wtHTT), suggesting that polyQ affects interaction with (de) ubiquitinating enzymes subsequent targeting soluble associated several ubiquitin-modifying enzymes, various have been identified are linked disease, either turnover affecting overall homeostasis. Here we describe their potential mechanism action toward improved towards proteostasis machinery.

Language: Английский

Citations

11

Arkadia and Ark2c Promote Substrate Ubiquitylation with Multiple E2 Enzymes DOI
Catherine L. Day, Claudia Roßig, Andrej Paluda

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0

UBA protein family: An emerging set of E1 ubiquitin ligases in cancer—A review DOI
Huhu Zhang,

Fulin Sun,

Hongyu Cao

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142277 - 142277

Published: March 1, 2025

Language: Английский

Citations

0

E2 conjugating enzymes: A silent but crucial player in Ubiquitin Biology DOI

Somya Parashar,

Aastha Kaushik, Rashmi K. Ambasta

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102740 - 102740

Published: April 1, 2025

Language: Английский

Citations

0