The migration behavior of human glioblastoma cells is influenced by the redox-sensitive human macrophage capping protein CAPG.

Autor: Prescher N; Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany., Hänsch S; Department of Biology, Center for Advanced Imaging (CAi), Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany., Knobbe-Thomsen CB; Department of Neuropathology, Heinrich-Heine University Düsseldorf and University Hospital, Universitätsstraße 1, 40225 Düsseldorf, Germany., Stühler K; Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany; Molecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany., Poschmann G; Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany. Electronic address: Gereon.Poschmann@uni-duesseldorf.de.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2021 May 01; Vol. 167, pp. 81-93. Date of Electronic Publication: 2021 Mar 10.
DOI: 10.1016/j.freeradbiomed.2021.02.038
Abstrakt: The macrophage capping protein CAPG belongs to the gelsolin superfamily which modulates actin dynamics by capping the growing end of actin filaments in a Ca 2+ - and PIP 2 -dependent manner resulting in polymerization inhibition of actin filaments. In the last years, additional functions for CAPG in transcription regulation were described and higher CAPG amounts have been linked to increased invasiveness and migration behavior in different human tumor entities like e.g. glioblastoma. Nevertheless, there is a lack of knowledge how additional functions of CAPG are regulated. As CAPG contains several cysteine residues which may be accessible to oxidation we were especially interested to investigate how alterations in the cysteine oxidation state may influence the function, localization, and regulation of CAPG. In the present study, we provide strong evidence that CAPG is a redox-sensitive protein and identified two cysteines: C282 and C290 as reversibly oxidized in glioblastoma cell lines. Whereas no evidence could be found that the canonical actin capping function of CAPG is redox-regulated, our results point to a novel role of the identified cysteines in the regulation of cell migration. Along with this, we found a localization shift out of the nucleus of CAPG and RAVER1, a potential interaction partner identified in our study which might explain the observed altered cell migration properties. The newly identified redox sensitive cysteines of CAPG could perspectively be considered as new targets for controlling tumor invasive properties.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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