Responsable/s del laboratorio
Head of lab
intro
Las proteínas son las efectoras de gran parte de las funciones fisiológicas en el interior de las células y su papel en el medio extracelular es fundamental. La función de las proteínas está a su vez finamente regulada a múltiples niveles que incluyen su síntesis y degradación, su localización intracelular y modificaciones postraduccionales. La modificación postraduccional de proteínas supone un mecanismo fundamental de regulación de su actividad biológica. Numerosos mediadores biológicos, entre los que se incluyen compuestos lipídicos y especies reactivas de oxígeno y nitrógeno, así como fármacos y toxinas, actúan modificando las proteínas. En nuestro grupo estamos interesados en los procesos de modificación postraduccional de proteínas, tanto desde el punto de vista de su importancia fisiológica, como de su papel en el mecanismo de acción de fármacos. Nuestro trabajo aborda varios aspectos: la caracterización estructural y funcional de nuevos tipos de modificación postraduccional, la identificación de nuevas dianas proteicas susceptibles de ser modificadas y el estudio de las potenciales repercusiones fisiopatológicas de estos fenómenos, fundamentalmente en el contexto de procesos inflamatorios y oncogénicos.
Miembros
| Dolores Pérez-Sala Gozalo |
| María de los Ángeles Pajares Tarancón |
| Alma Estefania Martinez Fernandez |
| Elena Hernandez Gerez |
| Paula Martinez Cenalmor |
| Patricia Gonzalez Jimenez |
| Nuria Goya Iglesias |
| Diego Moneo Corcuera |
| Elena Sala Lara |
| Anna Fernandez Bernal |
Publicaciones seleccionadas
González-Jiménez P, Duarte S, Martínez AE, Navarro-Carrasco E, Lalioti V, Pajares MA, Pérez-Sala D [2023]. Vimentin single cysteine residue acts as a tunable sensor for network organization and as a key for actin remodeling in response to oxidants and electrophiles. Redox Biol. 64, 102756. PMID: 37285743
Pajares MA, Hernández-Gerez E, Pekny M, Pérez-Sala D [2023]. Alexander disease: the road ahead. Neural Regen Res 18, 2156-2160. Doi: 10.4103/1673-5374.369097
Viedma-Poyatos A, González-Jiménez P, Pajares MA, Pérez-Sala D. [2022]. Alexander disease GFAP R239C mutant shows increased susceptibility to lipoxidation and elicits mitochondrial dysfunction and oxidative stress. Redox Biol 55: 102415. Doi: 10.1016/j.redox.2022.102415.
Lois-Bermejo I, González-Jiménez P, Duarte S, Pajares MA, Pérez-Sala D. [2022]. Vimentin tail segments are differentially exposed at distinct cellular locations and in response to stress. Front Cell Dev Biol. 10:908263. doi: 10.3389/fcell.2022.908263
Lalioti V, González-Sanz S, Lois-Bermejo I, González-Jiménez P, Viedma-Poyatos Á, Merino A, Pajares MA, Pérez-Sala D. [2022]. Cell surface detection of vimentin, ACE2 and SARS-CoV-2 Spike proteins reveals selective colocalization at primary cilia. Sci Rep. 12:7063. doi: 10.1038/s41598-022-11248-y.
Griesser E, Vemula V, Mónico A, Pérez-Sala D, Fedorova M. [2021]. Dynamic posttranslational modifications of cytoskeletal proteins unveil hot spots under nitroxidative stress. Redox Biol. 44, 102014.
Duarte S, Viedma-Poyatos A, Navarro-Carrasco E, Martínez, AE, Pajares, MA, Pérez-Sala D [2019]. Vimentin filaments interact with the actin cortex in mitosis allowing normal cell division. Nature Communications 10:4200
Mónico A, Guzmán-Caldentey J, Pajares MA, Martín-Santamaría S, Pérez-Sala D. [2021]. Molecular Insight into the Regulation of Vimentin by Cysteine Modifications and Zinc Binding. Antioxidants. 10:1039.
Monico A, Duarte S, Pajares MA, Pérez-Sala D [2019]. Vimentin disruption by lipoxidation and electrophiles: role of the cysteine residue and filament dynamics. Redox Biol. 23:101098. doi: 10.1016/j.redox.2019.101098
Ramos I, Stamatakis K, Oeste CL, Pérez-Sala D [2020]. Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections. Int J Mol Sci 21:4675. doi: 10.3390/ijms21134675.
Viedma-Poyatos Á, Pajares MA, Pérez-Sala D [2020]. Type III intermediate filaments as targets and effectors of electrophiles and oxidants. Redox Biol 36:101582. doi: 10.1016/j.redox.2020.101582
Pérez-Sala D, Oeste CL, Martínez AE, Carrasco, MJ, Garzón B, Cañada FJ [2015]. Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding. Nat Commun 6:7287
Díez-Dacal B, Sánchez-Gómez FJ, Sánchez-Murcia PA, Milackova I, Zimmerman T, Ballekova J, García-Martín E, Agúndez JA, Gharbi S, Gago F, Stefek M, Pérez-Sala D [2016]. Molecular interactions and implications of aldose reductase inhibition by PGA1 and clinically used prostaglandins. Mol Pharmacol. 89:42-52
Pérez-Sala D, Domingues R [2019]. Lipoxidation targets: from basic mechanisms to pathophysiology. Redox Biol. 23:101208. Doi: 10.1016/j.redox.2019.101208
Oeste CL, Pinar M, Schink KO, Martínez-Turrión J, Stenmark H, Peñalva MA, Pérez-Sala D [2014]. An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. PLoS ONE 9(9): e107190
Fondos
"From GFAP mutations in astrocytes to neurodegeneration: exploring a lipid-protein oxidation pathway" La Caixa Foundation HR21-00259 (awarded). https://fundacionlacaixa.org/es/convocatoria-caixaresearch-investigacion-salud-2021-proyecto-enfermedad-alexander
"The astrocyte nanofilament system in Alexander disease – from molecules to function, uncovering new leads for therapy” EJPRD2019-256 “ALEXANDER”. European Joint Program on Rare Diseases
“Validation of vimentin as a co-receptor for SARS-CoV-2 and intervention strategies”. CSIC PTI Global Health (PIE 202020E223/CSIC-COVID-19-100)
"Proteoforms in pathophysiology and drug action: focus on intermediate filament proteins and selected drug targets" Ministerio de Ciencia e Innovación RTI-2018-097624-B-I00 (cofunded FEDER).
This project aims at the characterization of protein modification by electrophilic lipid mediators and drugs with a special focus on intermediate filaments.
"Red de Reacciones Adversas a Alergenos y Fármacos (RIRAAF). Instituto de Salud Carlos III, Ref. RD16/0006/0021 . Duración, desde: 01/01/2017 hasta: 31/12/2021 Financiación: 107.937,50 €. Investigadora responsable (CIB-Margarita Salas): Dra. Mª Dolores Pérez-Sala Gozalo. Este proyecto fue co-financiado por el Instituto de Salud Carlos III y fondos FEDER de la UE"
Our contribution to this Network is focused on the identification and characterization of protein targets for haptenation by drugs, mainly beta-lactam antibiotics, and in providing knowledge for the assessment of their implications in drug allergy.
COST Action CA19105 EpiLipidNET "Pan-European Network in Lipidomics and Epilipidomics"
Más información
Incorporación:
Posibilidades de incorporación
Contactar para información sobre otras opciones.
Networking:
Synthetic Cell Initiative https://www.syntheticcell.eu/
Former networks:
EU Project 675132 (H2020-MSCA-ITN-2015). Innovative Training Network. "MASS Spectrometry TRaining network for Protein Lipid adduct Analysis". MASSTRPLAN. Oct 2015-Sept 2019.
COST Action CM1001 "Chemistry of non-enzymatic protein modification: modulation of protein structure and function"
COST: Action TD1304 Zinc-Net: the Network for the Biology of Zinc
COST Action CA15214 EUROCELLNET "An integrative action for multidisciplinary studies on cellular structural networks"
http://www.cost.eu/COST_Actions/ca/CA15214
- Red de Reacciones Adversas a Alergenos y Fármacos (RIRAAF) RETIC ISCIII. RD12/0013/0008
Patent applications:
- "Protein tag for endo-lysosomal localization and degradation". D. Pérez-Sala, P. Boya, K, Stamatakis. P200802721. September 25, 2008.
- "Compounds with 2-cyclopentenone structure as inhibitors of AKR family enzymes". D. Pérez-Sala, B. Díez. P201030449. March 25, 2010.
- “Use of 5-carboxymethyl-3-mercapto-1,2,4-triazino-[5,6-b]indoles and their pharmaceutical composition” Milan Stefek, Ivana Milackova, Beatriz Díez Dacal, Dolores Pérez-Sala Gozalo, Marta Soltesova-Prnova. WO2015/057175 A, 23-4-2015.