NIK as a Druggable Mediator of Tissue Injury.

MAP3K14 NIK TWEAK acute kidney injury apoptosis autoimmunity cell death chronic kidney disease cirrhosis diabetes epigenetic esteatohepatitis hepatitis inflammation mantle lymphoma myeloid leukemia osteoporosis sarcopenia verteporfin

Journal

Trends in molecular medicine
ISSN: 1471-499X
Titre abrégé: Trends Mol Med
Pays: England
ID NLM: 100966035

Informations de publication

Date de publication:
04 2019
Historique:
received: 05 12 2018
revised: 07 02 2019
accepted: 13 02 2019
pubmed: 31 3 2019
medline: 13 2 2020
entrez: 31 3 2019
Statut: ppublish

Résumé

NF-κB-inducing kinase (NIK, MAP3K14) is best known as the apical kinase that triggers non-canonical NF-κB activation and by its role in the immune system. Recent data indicate a role for NIK expressed by non-lymphoid cells in cancer, kidney disease, liver injury, glucose homeostasis, osteosarcopenia, vascular calcification, hematopoiesis, and endothelial function. The spectrum of NIK-associated disease now ranges from immunodeficiency (when NIK is defective) to autoimmunity, cancer, sterile inflammation, fibrosis, and metabolic disease when NIK is overactive. The development of novel small-molecule NIK inhibitors has paved the way to test NIK targeting to treat disease in vivo, and may eventually lead to NIK targeting in the clinic. In addition, NIK activators are being explored for specific conditions such as myeloid leukemia.

Identifiants

pubmed: 30926358
pii: S1471-4914(19)30040-1
doi: 10.1016/j.molmed.2019.02.005
pii:
doi:

Substances chimiques

Biomarkers 0
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

341-360

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Lara Valiño-Rivas (L)

Department of Nephrology and Hypertension, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, School of Medicine, Universidad Autónoma de Madrid (UAM), Red de Investigación Renal (REDINREN), and Fundación Renal Íñigo Álvarez de Toledo (FRIAT), Madrid, Spain.

Juan José Vaquero (JJ)

Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcala and REDINREN, Madrid, Spain.

David Sucunza (D)

Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcala and REDINREN, Madrid, Spain.

Sara Gutierrez (S)

Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcala and REDINREN, Madrid, Spain.

Ana B Sanz (AB)

Department of Nephrology and Hypertension, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, School of Medicine, Universidad Autónoma de Madrid (UAM), Red de Investigación Renal (REDINREN), and Fundación Renal Íñigo Álvarez de Toledo (FRIAT), Madrid, Spain.

Manuel Fresno (M)

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas de la UAM, Madrid, Spain.

Alberto Ortiz (A)

Department of Nephrology and Hypertension, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, School of Medicine, Universidad Autónoma de Madrid (UAM), Red de Investigación Renal (REDINREN), and Fundación Renal Íñigo Álvarez de Toledo (FRIAT), Madrid, Spain; These authors contributed equally. Electronic address: aortiz@fjd.es.

Maria Dolores Sanchez-Niño (MD)

Department of Nephrology and Hypertension, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, School of Medicine, Universidad Autónoma de Madrid (UAM), Red de Investigación Renal (REDINREN), and Fundación Renal Íñigo Álvarez de Toledo (FRIAT), Madrid, Spain; These authors contributed equally. Electronic address: mdsanchez@fjd.es.

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Classifications MeSH