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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Monomeric ubiquitin (Ub) is a 76-amino-acid highly conserved protein found in eukaryotes. The biological activity of Ub first described in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations, compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes, have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, and cardio- and brain-protective agent.

Details

Title
Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb)
Author
Mendoza-Salazar, Ivette 1   VIAFID ORCID Logo  ; Fragozo, Ana 1 ; González-Martínez, Aneth P 1 ; Trejo-Martínez, Ismael 1 ; Arreola, Rodrigo 2   VIAFID ORCID Logo  ; Pavón, Lenin 3 ; Almagro, Juan C 4 ; Vallejo-Castillo, Luis 5 ; Aguilar-Alonso, Francisco A 5 ; Pérez-Tapia, Sonia M 1   VIAFID ORCID Logo 

 Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico; [email protected] (I.M.-S.); [email protected] (A.F.); [email protected] (A.P.G.-M.); [email protected] (I.T.-M.); [email protected] (J.C.A.); [email protected] (L.V.-C.); Laboratorio Nacional para Servicios Especializados de Investigación, Desarrollo e Innovación (I + D + i) para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico 
 Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Colonia San Lorenzo Huipulco, Tlalpan, Mexico City 14370, Mexico; [email protected] 
 Laboratorio de Psicoinmunología, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico; [email protected] 
 Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico; [email protected] (I.M.-S.); [email protected] (A.F.); [email protected] (A.P.G.-M.); [email protected] (I.T.-M.); [email protected] (J.C.A.); [email protected] (L.V.-C.); Laboratorio Nacional para Servicios Especializados de Investigación, Desarrollo e Innovación (I + D + i) para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico; GlobalBio, Inc., 320 Concord Ave, Cambridge, MA 02138, USA 
 Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico; [email protected] (I.M.-S.); [email protected] (A.F.); [email protected] (A.P.G.-M.); [email protected] (I.T.-M.); [email protected] (J.C.A.); [email protected] (L.V.-C.); Laboratorio Nacional para Servicios Especializados de Investigación, Desarrollo e Innovación (I + D + i) para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás, Alcaldía Miguel Hidalgo, Mexico City 11340, Mexico 
First page
185
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
14248247
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2930984597
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.