Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners

Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla, Carmelo Bernabeu

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalCells
Volume8
Issue number9
DOIs
StatePublished - Sep 13 2019

Keywords

  • BMP
  • HHT
  • TGF-β
  • TRIM family
  • cancer
  • endoglin
  • endothelial cells
  • galectin family
  • preeclampsia
  • protein–protein interactions

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Endoglin Protein Interactome Profiling Identifies TRIM21 and Galectin-3 as New Binding Partners'. Together they form a unique fingerprint.

Cite this