Phosphoglycerate Mutase 1 Activates DNA Damage Repair via Regulation of WIP1 Activity.

Animals Apoptosis / genetics Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics DNA Damage / physiology DNA Repair / genetics Female Humans Male Mice Phosphoglycerate Mutase / genetics Protein Phosphatase 2C / genetics
DNA damage repair PGAM1 WIP1 glioma irradiation temozolomide

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
14 04 2020
Historique:
received: 29 05 2019
revised: 18 12 2019
accepted: 25 03 2020
entrez: 16 4 2020
pubmed: 16 4 2020
medline: 28 4 2021
Statut: ppublish

Résumé

The metabolic enzyme phosphoglycerate mutase 1 (PGAM1) is overexpressed in several types of cancer, suggesting an additional function beyond its established role in the glycolytic pathway. We here report that PGAM1 is overexpressed in gliomas where it increases the efficiency of the DNA damage response (DDR) pathway by cytoplasmic binding of WIP1 phosphatase, thereby preventing WIP1 nuclear translocation and subsequent dephosphorylation of the ATM signaling pathway. Silencing of PGAM1 expression in glioma cells consequently decreases formation of γ-H2AX foci, increases apoptosis, and decreases clonogenicity following irradiation (IR) and temozolomide (TMZ) treatment. Furthermore, mice intracranially implanted with PGAM1-knockdown cells have significantly improved survival after treatment with IR and TMZ. These effects are counteracted by exogenous expression of two kinase-dead PGAM1 mutants, H186R and Y92F, indicating an important non-enzymatic function of PGAM1. Our findings identify PGAM1 as a potential therapeutic target in gliomas.

Identifiants

DOI: 10.1016/j.celrep.2020.03.082 PMID: 32294440
pubmed: 32294440
pii: S2211-1247(20)30417-4
doi: 10.1016/j.celrep.2020.03.082
pii:
doi:

Substances chimiques

PPM1D protein, human EC 3.1.3.16
Protein Phosphatase 2C EC 3.1.3.16
Phosphoglycerate Mutase EC 5.4.2.11
phosphoglycerate mutase 1, human EC 5.4.2.11

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107518

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Shigeo Ohba (S)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurosurgery, Fujita Health University, Toyoake, Aichi, Japan.

Tor-Christian Aase Johannessen (TA)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway.

Kamalakar Chatla (K)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.

Xiaodong Yang (X)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.

Russell O Pieper (RO)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.

Joydeep Mukherjee (J)

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: joydeep.mukherjee@ucsf.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Phénomènes génétiques › Réparation de l'ADN › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Isomerases › Intramolecular transferases › Phosphotransferases phosphomutases › Phosphoglyceromutase › Phosphoglycerate Mutase 1 Activates DNA Damage...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphoprotein Phosphatases › Protein phosphatase 2C › Phosphoglycerate Mutase 1 Activates DNA Damage...