Disrupting the LC3 Interaction Region (LIR) Binding of Selective Autophagy Receptors Sensitizes AML Cell Lines to Cytarabine.

AML – acute myeloid leukemia LIR interaction cytarabine inhibitors phage display selective autophagy receptor short linear motifs (SLiMs)

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2020
Historique:
received: 11 12 2019
accepted: 10 03 2020
entrez: 17 4 2020
pubmed: 17 4 2020
medline: 17 4 2020
Statut: epublish

Résumé

Short linear motifs (SLiMs) located in disordered regions of multidomain proteins are important for the organization of protein-protein interaction networks. By dynamic association with their binding partners, SLiMs enable assembly of multiprotein complexes, pivotal for the regulation of various aspects of cell biology in higher organisms. Despite their importance, there is a paucity of molecular tools to study SLiMs of endogenous proteins in live cells. LC3 interacting regions (LIRs), being quintessential for orchestrating diverse stages of autophagy, are a prominent example of SLiMs and mediate binding to the ubiquitin-like LC3/GABARAP family of proteins. The role of LIRs ranges from the posttranslational processing of their binding partners at early stages of autophagy to the binding of selective autophagy receptors (SARs) to the autophagosome. In order to generate tools to study LIRs in cells, we engineered high affinity binders of LIR motifs of three archetypical SARs: OPTN, p62, and NDP52. In an array of

Identifiants

pubmed: 32296703
doi: 10.3389/fcell.2020.00208
pmc: PMC7137635
doi:

Types de publication

Journal Article

Langues

eng

Pagination

208

Informations de copyright

Copyright © 2020 Putyrski, Vakhrusheva, Bonn, Guntur, Vorobyov, Brandts, Dikic and Ernst.

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Auteurs

Mateusz Putyrski (M)

Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt, Germany.
Project Group Translational Medicine and Pharmacology, Fraunhofer Institute for Molecular Biology and Applied Ecology, Frankfurt, Germany.

Olesya Vakhrusheva (O)

Department of Medicine, Hematology/Oncology, Goethe-University, Frankfurt, Germany.

Florian Bonn (F)

Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt, Germany.

Suchithra Guntur (S)

Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt, Germany.

Andrew Vorobyov (A)

Project Group Translational Medicine and Pharmacology, Fraunhofer Institute for Molecular Biology and Applied Ecology, Frankfurt, Germany.

Christian Brandts (C)

Department of Medicine, Hematology/Oncology, Goethe-University, Frankfurt, Germany.
German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany.
University Cancer Center Frankfurt, Goethe-University, Frankfurt, Germany.

Ivan Dikic (I)

Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt, Germany.
Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.

Andreas Ernst (A)

Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt, Germany.
Project Group Translational Medicine and Pharmacology, Fraunhofer Institute for Molecular Biology and Applied Ecology, Frankfurt, Germany.

Classifications MeSH