Post-translational modifications (PTMs) by members of the ubiquitin-like family (UbL) are essential for cell survival and for the proper function of organisms. Cellular signaling drives conserved enzymatic pathways that add UbL modifiers to target proteins determining their fate, including changes in protein-protein interactions, localization, or stability and degradation. UbL modifications are important for proper development and maintaining homeostasis in adults. UbL-based dysfunction is implicated in many illnesses (cancer, diabetes, neurodegeneration), including rare diseases.
A low prevalence or rare disease is defined as one with a prevalence of less than 1 case per 2000 inhabitants. It is estimated that there are between 5,000 and 7,000 different rare diseases, some of which affect a small number of people around the world. However, considering the various pathologies, it is calculated that between 6 and 8% of the world population would be afflicted by any of these diseases. Therefore, an estimated 30 million Europeans suffer from various rare diseases. We are interested in the impact of protein homeostasis deregulation in rare diseases; one example is Townes-Brocks Syndrome (TBS), affecting digit formation, kidney function and hearing. We explore the role of UbL-based regulation in TBS and other low prevalence diseases.
Research line 1: Regulation of post-translational modifications by members of the ubiquitin-like family
Despite their relevance in physiology and diseases, studying UbL modifications is particularly challenging because they are normally transient and occur in a small percentage of a given protein pool. To overcome these difficulties, we develop specific strategies, including BioUbL (Sci Reports 2017), to capture and identify UbL-modified proteins using in vivo biotinylation; UbL-ID (Nat Comm 2021), to identify interactors of a given protein of interest when modified by UbLs; or BioE3 (Nat Com 2023), to identify specific targets of E3 ligases. E3 ligases give specificity to the UbL system as they recognize specific targets. There are more than 600 E3 ligases and in most of the cases, targets are largely unknown. E3s are particularly relevant as they are key players in the emerging strategies of targeted protein degradation (TPD), therefore knowing endogenous targets can inform on specificity and off-targets of designed TPD drugs.
Research line 2: Proteostasis regulation in rare diseases
We are interested in understanding the mechanisms underlying TBS and other diseases related to the UbL family (e.g. Angelman Syndrome, Opitz GBBB Syndrome). Individuals with TBS, caused by mutations in the transcription factor SALL1, show anomalies in cilia formation and function due to the interaction of mutant SALL1 proteins with centrosomal/ciliary factors (Am J Human Genet 2018; eLife 2020). We investigate the relationship of mutations with the protein homeostasis regulation of LUZP1, an interactor of mutated SALL1. We also study the relationship of other rare diseases with components of the UbL family, such as E3 ligases.
Collaborations
Arkaitz Carracedo, June Ereño, Juan Manuel Falcón and Malu Martínez-Chantar (CIC bioGUNE, Spain), Ugo Mayor and Josean Rodríaguez (UPV/EHU, Spain), Orhi Barroso Gomila (Biobizkaia, Spain), Carmen Rivas (CIMUS, Santiago de Compostela, Spain), Carles Galdeano and Jordi Jiménez (University of Barcelona, Spain), Jordi Torres (University of Lleida, Spain), Manuel S Rodríguez (CNRS, France), Alfred Vertegaal (LUMC, Netherlands), Simona Polo (IFOM, Italy), Germana Meroni (University of Trieste, Italy), Tim Clausen (IMP, Austria), Nicolas Bidère (Inserm, France), Mikko Taipale (University of Toronto, Canada).
Links
Webpage: https://www.rosabarriolab.es/
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Group Leader
Rosa Barrio
Associate Principal Investigator -
James D Sutherland
TECHNICIANS / DOCTORAL CANDIDATES -
Laura Merino Cacho
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Mónica Pozo Rodríguez
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Sandra Cano López
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Claudia Guinea Perez
Members
Latest Publications
Role of TRIM24 in the regulation of proteasome-autophagy crosstalk in bortezomib-resistant mantle cell lymphoma
Bouvier, C; Gonzalez-Santamarta, M; Profitós-Pelejà, N; Armengol, M; Quinet, G; Alasseur, Q; Ceccato, L; Xolalpa, W; Freire, R; Guillermet-Guibert, J; Reybier, K; Caminade, AM; Beck, HC; Carvalho, ...
CELL DEATH DISCOVERY
2025-03-17
Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome
Merino-Cacho, L; Barroso-Gomila, O; Pozo-Rodríguez, M; Muratore, V; Guinea-Pérez, C; Serrano, A; Pérez, C; Cano-López, S; Urcullu, A; Azkargorta, M; Iloro, I; Galdeano, C; Juárez-Jiménez, J; ...
CELL COMMUNICATION AND SIGNALING
2025-02-19
Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway
Gil-Pitarch, C; Serrano-Maciá, M; Simon, J; Mosca, L; Conter, C; Rejano-Gordillo, CM; Zapata-Pavas, LE; Peña-Sanfélix, P; Azkargorta, M; Rodríguez-Agudo, R; Lachiondo-Ortega, S; Mercado-Gómez, ...
CELL REPORTS MEDICINE
2024-07-16
Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination
Ayuso-García, P; Sánchez-Rueda, A; Velasco-Avilés, S; Tamayo-Caro, M; Ferrer-Pinós, A; Huarte-Sebastian, C; Alvarez, V; Riobello, C; Jiménez-Vega, S; Buendia, I; Cañas-Martin, J; Fernández-Susavila, ...
SCIENCE ADVANCES
2024-04-12
SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
Lachiondo-Ortega, S; Rejano-Gordillo, CM; Simon, J; Lopitz-Otsoa, F; Delgado, TC; Mazan-Mamczarz, K; Goikoetxea-Usandizaga, N; Zapata-Pavas, LE; García-del Río, A; Guerra, P; Peña-Sanfélix, ...
CELL REPORTS
2024-03-26
SUMOylation modulates eIF5A activities in both yeast and pancreatic ductal adenocarcinoma cells
Seoane, R; Lama-Diaz, T; Romero, AM; El Motiam, A; Martinez-Ferriz, A; Vidal, S; Bouzaher, YH; Blanquer, M; Tolosa, RM; Mewa, JC; Rodriguez, MS; Garcia-Sastre, A; Xirodimas, D; Sutherland, JD; ...
CELLULAR & MOLECULAR BIOLOGY LETTERS
2024-01-16
Biotin-based strategies to explore the world of ubiquitin and ubiquitin-like modifiers
Merino-Cacho, L; Barroso-Gomila, O; Hernandez-Sánchez, S; Ramirez, J; Mayor, U; Sutherland, JD; Barrio, R;
CHEMBIOCHEM
2024-01-05
BioE3 identifies specific substrates of ubiquitin E3 ligases
Barroso-Gomila, O; Merino-Cacho, L; Muratore, V; Perez, C; Taibi, V; Maspero, E; Azkargorta, M; Iloro, I; Trulsson, F; Vertegaal, ACO; Mayor, U; Elortza, F; Polo, S; Barrio, R; Sutherland, JD; ...
NATURE COMMUNICATIONS
2023-11-23
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Lenza, MP; Egia-Mendikute, L; Antoñana-Vildosola, A; Soares, CO; Coelho, H; Corzana, F; Bosch, A; Manisha, P; Quintana, JI; Oyenarte, I; Unione, L; Moure, MJ; Azkargorta, M; Atxabal, U; Sobczak, ...
NATURE COMMUNICATIONS
2023-06-13
Studying the ubiquitin code through biotin-based labelling methods
Barroso-Gomila, O; Muratore, V; Merino-Cacho, L; Rodriguez, JA; Barrio, R; Sutherland, JD;
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
2022-11-16
In memoriam: Huib Ovaa, the brain behind the formula (18/12/1973-19/05/2020)
Barrio, R; Rodriguez, MS;
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
2022-11-16
U1A is a positive regulator of the expression of heterologous and cellular genes involved in cell proliferation and migration
Rovira, E; Moreno, B; Razquin, N; Hjerpe, R; Gonzalez-Lopez, M; Barrio, R; de los Mozos, IR; Ule, J; Pastor, F; Blazquez, L; Fortes, P;
MOLECULAR THERAPY NUCLEIC ACIDS
2022-05-25
Editorial: 17th Spanish Society for Developmental Biology Meeting: New Trends in Developmental Biology
Araujo, SJ; Barrio, R;
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2022-04-20
Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease
Parra-Peralbo, E; Talamillo, A; Barrio, R;
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2021-12-21
A Genotyped Case of Townes-Brocks Syndrome with Absent Pulmonary Valve Syndrome from Turkey
Ilhan, O; Gumus, E; Hakan, N; Istar, H; Harmandar, B; Olgun, H; Karakus, SC; Cullu, N; Kohlhase, J; Sutherland, JD; Barrio, R;
JOURNAL OF PEDIATRIC GENETICS
2021-12-10
Identification of proximal SUMO-dependent interactors using SUMO-ID
Barroso-Gomila, O; Trulsson, F; Muratore, V; Canosa, I; Merino-Cacho, L; Cortazar, AR; Pérez, C; Azkargorta, M; Iloro, I; Carracedo, A; Aransay, AM; Elortza, F; Mayor, U; Vertegaal, ACO; Barrio, ...
NATURE COMMUNICATIONS
2021-11-18
NEDDYLATION INHIBITION REDUCES LIVER STEATOSIS IN MAFLD MICE MODELS BY PROMOTING HEPATIC FATTY ACID OXIDATION VIA DEPTOR-mTOR AXIS
Serrano-Maciá, M; Espinosa, JS; González-Rellan, MJ; Azkargorta, M; Goikoetxea-Usandizaga, N; Lopitz-Otsoa, F; De Urturi, DS; Agudo, RR; Lachiondo-Ortega, S; Mercado-Gómez, M; Bizkarguenaga, ...
HEPATOLOGY
2021-10-01
SALL1 Modulates CBX4 Stability, Nuclear Bodies, and Regulation of Target Genes
Giordano, I; Pirone, L; Muratore, V; Landaluze, E; Pérez, C; Lang, V; Garde-Lapido, E; Gonzalez-Lopez, M; Barroso-Gomila, O; Vertegaal, ACO; Aransay, AM; Rodriguez, JA; Rodriguez, MS; Sutherland, ...
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2021-09-21
Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis
Serrano-Maciá, M; Simón, J; González-Rellan, MJ; Azkargorta, M; Goikoetxea-Usandizaga, N; Lopitz-Otsoa, F; De Urturi, DS; Rodríguez-Agudo, R; Lachiondo-Ortega, S; Mercado-Gomez, M; de Juan, ...
MOLECULAR METABOLISM
2021-07-13
LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
Bozal-Basterra, L; Gonzalez-Santamarta, M; Muratore, V; Martín-Martín, N; Ercilla, A; Rodríguez, JA; Carracedo, A; Sutherland, JD; Barrio, R;
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2021-04-01