Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners
Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastroi...
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1082 |
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| author | Eunate Gallardo-Vara Lidia Ruiz-Llorente Juan Casado-Vela María J. Ruiz-Rodríguez Natalia López-Andrés Asit K. Pattnaik Miguel Quintanilla Carmelo Bernabeu |
| author_facet | Eunate Gallardo-Vara Lidia Ruiz-Llorente Juan Casado-Vela María J. Ruiz-Rodríguez Natalia López-Andrés Asit K. Pattnaik Miguel Quintanilla Carmelo Bernabeu |
| author_sort | Eunate Gallardo-Vara |
| collection | DOAJ |
| description | Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectases, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-β receptor complex and the extracellular region of endoglin has been shown to interact with types I and II TGF-β receptors, as well as with BMP9 and BMP10 ligands, both members of the TGF-β family. To search for novel protein interactors, we screened a microarray containing over 9000 unique human proteins using recombinant sEng as bait. We find that sEng binds with high affinity, at least, to 22 new proteins. Among these, we validated the interaction of endoglin with galectin-3, a secreted member of the lectin family with capacity to bind membrane glycoproteins, and with tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin-protein ligase. Using human endothelial cells and Chinese hamster ovary cells, we showed that endoglin co-immunoprecipitates and co-localizes with galectin-3 or TRIM21. These results open new research avenues on endoglin function and regulation. |
| first_indexed | 2024-03-12T10:40:47Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:40:47Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7ded8255c2cc400e8cc168fc3a811ab12023-09-02T08:11:25ZengMDPI AGCells2073-44092019-09-0189108210.3390/cells8091082cells8091082Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding PartnersEunate Gallardo-Vara0Lidia Ruiz-Llorente1Juan Casado-Vela2María J. Ruiz-Rodríguez3Natalia López-Andrés4Asit K. Pattnaik5Miguel Quintanilla6Carmelo Bernabeu7Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainCentro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainBioengineering and Aerospace Engineering Department, Universidad Carlos III and Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Leganés, 28911 Madrid, SpainCentro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainCardiovascular Translational Research, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), IdiSNA, 31008 Pamplona, SpainSchool of Veterinary Medicine and Biomedical Sciences, and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USAInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC), and Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainCentro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, SpainEndoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectases, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-β receptor complex and the extracellular region of endoglin has been shown to interact with types I and II TGF-β receptors, as well as with BMP9 and BMP10 ligands, both members of the TGF-β family. To search for novel protein interactors, we screened a microarray containing over 9000 unique human proteins using recombinant sEng as bait. We find that sEng binds with high affinity, at least, to 22 new proteins. Among these, we validated the interaction of endoglin with galectin-3, a secreted member of the lectin family with capacity to bind membrane glycoproteins, and with tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin-protein ligase. Using human endothelial cells and Chinese hamster ovary cells, we showed that endoglin co-immunoprecipitates and co-localizes with galectin-3 or TRIM21. These results open new research avenues on endoglin function and regulation.https://www.mdpi.com/2073-4409/8/9/1082endothelial cellsendoglinTGF-βBMPHHTcancerpreeclampsiaTRIM familygalectin familyprotein–protein interactions |
| spellingShingle | Eunate Gallardo-Vara Lidia Ruiz-Llorente Juan Casado-Vela María J. Ruiz-Rodríguez Natalia López-Andrés Asit K. Pattnaik Miguel Quintanilla Carmelo Bernabeu Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners Cells endothelial cells endoglin TGF-β BMP HHT cancer preeclampsia TRIM family galectin family protein–protein interactions |
| title | Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners |
| title_full | Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners |
| title_fullStr | Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners |
| title_full_unstemmed | Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners |
| title_short | Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners |
| title_sort | endoglin protein interactome profiling identifies trim21 and galectin 3 as new binding partners |
| topic | endothelial cells endoglin TGF-β BMP HHT cancer preeclampsia TRIM family galectin family protein–protein interactions |
| url | https://www.mdpi.com/2073-4409/8/9/1082 |
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