Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF-κB signaling.


Journal

Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516

Informations de publication

Date de publication:
12 02 2019
Historique:
received: 12 12 2018
accepted: 26 12 2018
pubmed: 7 1 2019
medline: 5 11 2019
entrez: 7 1 2019
Statut: ppublish

Résumé

Nuclear factor-κB (NF-κB) is a crucial transcription factor family involved in the regulation of immune and inflammatory responses and cell survival. The linear ubiquitin chain assembly complex (LUBAC), composed of the HOIL-1L, HOIP, and SHARPIN subunits, specifically generates Met1-linked linear ubiquitin chains through the ubiquitin ligase activity in HOIP, and activates the NF-κB pathway. We recently identified a chemical inhibitor of LUBAC, which we named HOIPIN-1 (HOIP inhibitor-1). To improve the potency of HOIPIN-1, we synthesized 7 derivatives (HOIPIN-2∼8), and analyzed their effects on LUBAC and NF-κB activation. Among them, HOIPIN-8 suppressed the linear ubiquitination activity by recombinant LUBAC at an IC

Identifiants

pubmed: 30611571
pii: S0006-291X(18)32846-8
doi: 10.1016/j.bbrc.2018.12.164
pii:
doi:

Substances chimiques

Anti-Inflammatory Agents 0
Cytokines 0
NF-kappa B 0
Small Molecule Libraries 0
Transcription Factors 0
Ubiquitin 0
RBCK1 protein, human EC 2.3.2.27
RNF31 protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

700-706

Informations de copyright

Copyright © 2018 Elsevier Inc. All rights reserved.

Auteurs

Ken Katsuya (K)

Biological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Daisuke Oikawa (D)

Department of Pathobiochemistry, Graduate School of Medicine, Osaka City University, Osaka, 545-8585, Japan.

Kiyosei Iio (K)

Chemical Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Shingo Obika (S)

Chemical Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Yuji Hori (Y)

Biological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Toshiki Urashima (T)

Biological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Kumiko Ayukawa (K)

Biological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka, 569-1125, Japan.

Fuminori Tokunaga (F)

Department of Pathobiochemistry, Graduate School of Medicine, Osaka City University, Osaka, 545-8585, Japan. Electronic address: ftokunaga@med.osaka-cu.ac.jp.

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Classifications MeSH