Proteins are effectors of most physiological functions in cells and they play a key role in the extracellular medium. Protein function is finely tuned at multiple levels including synthesis and degradation, intracellular localization and posttranslational modifications. The posttranslational modification of proteins is a key mechanism for the regulation of their biological activity. Various biological mediators, including lipids and reactive oxygen and nitrogen species, and also some drugs and toxins, can modify proteins posttranslationally. We are interested in the study of the importance of these processes in molecular pathophysiology and in the mechanisms of drug action. Our work includes several aspects: the structural and functional characterization of novel types of posttranslational modifications, the identification of novel protein targets for modification and the study of the pathophysiological consequences of these phenomena, mainly in the context of inflammatory and oncogenic processes.
CURRENT MEMBERS OF THE RESEARCH TEAM:
Dolores Pérez-Sala; María A. Pajares; Álvaro Viedma Poyatos; Silvia González Sanz
Duarte S, Viedma-Poyatos A, Navarro-Carrasco E, Martínez, AE, Pajares, MA, Pérez-Sala D . Vimentin filaments interact with the actin cortex in mitosis allowing normal cell division. Nature Communications 10:4200
Pérez-Sala D, Domingues R . Lipoxidation targets: from basic mechanisms to pathophysiology. Redox Biol. Doi: 10.1016/j.redox.2019.101208
Monico A, Duarte S, Pajares MA, Pérez-Sala D . Vimentin disruption by lipoxidation and electrophiles: role of the cysteine residue and filament dynamics. Redox Biol. doi: 10.1016/j.redox.2019.101098
Viedma-Poyatos A, de Pablo Y, Pekny M, Pérez-Sala D . The cysteine residue of glial fibrillary acidic protein is a critical target for lipoxidation and required for efficient network organization. Free Rad Biol Med. DOI: 10.1016/j.freeradbiomed.2018.04.007
Pajares MA, Pérez-Sala D . Mammalian sulfur amino acid metabolism: a nexus between redox regulation, nutrition, epigenetics and detoxification. Antioxid Redox Signal. doi: 10.1089/ars.2017.7237
Sánchez-Gómez FJ, González-Morena J, Vida Y, Pérez-Inestrosa E, Blanca M, Torres MJ, Pérez-Sala D . Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells. Allergy. DOI: 10.1111/all.12958
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 . Molecular interactions and implications of aldose reductase inhibition by PGA1 and clinically used prostaglandins. Mol Pharmacol. 89:42-52
Pérez-Sala D, Oeste CL, Martínez AE, Carrasco, MJ, Garzón B, Cañada FJ . Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding. Nat Commun 6:7287
Aldini G, Domingues RM, Spickett CM, Domingues P, Altomare A, Sánchez-Gómez FJ, Oeste CL, Pérez-Sala D . Protein lipoxidation: Detection strategies and challenges. Redox Biol 5:253-266
Oeste CL, Pinar M, Schink KO, Martínez-Turrión J, Stenmark H, Peñalva MA, Pérez-Sala D . An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. PLoS ONE 9(9): e107190
Delgado M, Garrido F, Pérez-Miguelsanz J, Pacheco M, Partearroyo T, Pérez-Sala D, Pajares MA . Acute liver injury induces nucleocytoplasmic redistribution of hepatic methionine metabolism enzymes. Antioxid Redox Signal 20:2541-2554
Oeste CL, Martínez-López M, Pérez-Sala D . Taking a lipidation-dependent path toward endolysosomes. Commun Integr Biol. 8:5, e1078041
Duarte S, Viedma-Poyatos A, Navarro-Carrasco E, Martínez AE, Pajares MA, Pérez-Sala D . Vimentin filaments interact with the mitotic cortex allowing normal cell division. BioRriv. DOI: https://doi.org/10.1101/356642
EU Project 675132 (H2020-MSCA-ITN-2015). Innovative Training Network. "MASS Spectrometry TRaining network for Protein Lipid adduct Analysis". MASSTRPLAN. Oct 2015-Sept 2019.
"Proteoforms in pathophysiology and drug action: focus on intermediate filament proteins and selected drug targets" Ministerio de Ciencia, Innovación y Universidades RTI-2018-097624-B-I00 (cofunded FEDER).
"Protein modification by lipoxidation and drug addition: novel perspectives for exploring disease mechanisms and therapeutic strategies" MINECO SAF2015-68590-R (cofunded FEDER).
Network for the Research on Asthma, Adverse and Allergic Reactions (ARADyAL). Instituto de Salud Carlos III. RETIC RD16/0006/0021.
COST Action CA15214 EUROCELLNET "An integrative action for multidisciplinary studies on cellular structural networks"
COST Action CM1001 "Chemistry of non-enzymatic protein modification: modulation of protein structure and function"
Acción COST (European Cooperation in the field of Scientific and Technical Research): Action TD1304 Zinc-Net: the Network for the Biology of Zinc
- "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 ALR family enzymes". D. Pérez-Sala, B. Díez. P201030449. March 25, 2010.
- EU COST Action CM1001: Chemistry of non-enzymatic protein modification- modulation of protein structure and function. http://users.unimi.it/cm1001/
- Red de Reacciones Adversas a Alergenos y Fármacos (RIRAAF) RETIC ISCIII. RD12/0013/0008