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The E3 ubiquitin ligase MARCH 3 controls the endothelial barrier
Author(s) -
Leclair Héloïse M.,
AndréGrégoire Gwennan,
Treps Lucas,
Azzi Sandy,
Bidère Nicolas,
Gavard Julie
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12417
Subject(s) - microbiology and biotechnology , occludin , ubiquitin ligase , gene silencing , downregulation and upregulation , transcriptome , ubiquitin , endosome , endothelial stem cell , biology , barrier function , small interfering rna , transcription factor , tight junction , chemistry , rna , gene expression , gene , biochemistry , intracellular , in vitro
Cell–cell contacts coordinate the endothelial barrier function in response to external cues. To identify new mediators involved in cytokine‐promoted endothelial permeability, we screened a si RNA library targeting E3 ubiquitin ligases. Here, we report that silencing of the late endosome/lysosomal membrane‐associated RING ‐ CH ‐3 ( MARCH 3) enzyme protects the endothelial barrier. Furthermore, transcriptome analysis unmasked the upregulation of the tight junction‐encoding gene occludin ( OCLN ) in MARCH 3‐depleted cells. Indeed, MARCH 3 silencing results in the strengthening of cell‐cell contacts, as evidenced by the accumulation of junctional proteins. From a molecular standpoint, the FoxO1 forkhead transcription repressor was inactivated in the absence of MARCH 3. This provides a possible molecular link between MARCH 3 and the signaling pathway involved in regulating the expression of junctional proteins and barrier integrity.