Type III intermediate filaments as targets and effectors of electrophiles and oxidants
| Autor: | Dolores Pérez-Sala, María A. Pajares, Álvaro Viedma-Poyatos |
|---|---|
| Přispěvatelé: | Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, Viedma-Poyatos, Álvaro [0000-0003-4920-6328], Pajares, María A. [0000-0002-4714-9051], Pérez-Sala, Dolores [0000-0003-0600-665X], Viedma-Poyatos, Álvaro, Pajares, María A., Pérez-Sala, Dolores |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Redox sensing Clinical Biochemistry Intermediate Filaments Vimentin macromolecular substances Review Article Biochemistry Desmin Protein filament 03 medical and health sciences 0302 clinical medicine Glial Fibrillary Acidic Protein Intermediate filament lcsh:QH301-705.5 Cytoskeleton lcsh:R5-920 Glial fibrillary acidic protein biology Chemistry GFAP Organic Chemistry Peripherin Oxidants Cell biology Lipoxidation 030104 developmental biology Aggresome lcsh:Biology (General) biology.protein Cysteine oxidative modifications lcsh:Medicine (General) 030217 neurology & neurosurgery Cysteine |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Redox Biology Redox Biology, Vol 36, Iss, Pp 101582-(2020) |
| Popis: | 16 p.-5 fig. Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications,elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target. This work was supported by Grants from Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación (MCI, Spain) and European Regional Development Fund, RTI2018-097624-B-I00,Instituto de Salud Carlos III (Spain) RETIC AraDyal RD16/0006/0021,and CSIC PTI Global Health (PIE202020E223/CSIC-COV19-100). AV-P is supported by the FPI program from MCI, reference BES-2016-076965. |
| Databáze: | OpenAIRE |
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