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Inhibition of the HEG1-KRIT1 interaction increases KLF4 and KLF2 expression in endothelial cells

FASEB Bioadv. 2021-02; 
Miguel Alejandro Lopez-Ramirez, Sara McCurdy, Wenqing Li, Mark K Haynes, Preston Hale, Karol Francisco, Killian Oukoloff, Matthew Bautista, Chelsea H J Choi, Hao Sun, Brendan Gongol, John Y Shyy, Carlo Ballatore, Larry A Sklar, Alexandre R Gingras
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Mutagenesis Services … Synthetic human non- biotinylated HEG1 7- mer peptide (residues 1375– 1381) was purchased from GenScript. His6- EGFP- KRIT1 (WT) FERM domain (417– 736) and KRIT1(L717,721A) mutant were cloned into pETM- 11 and expressed in BL21 Star (DE3) … Get A Quote

摘要

The transmembrane protein heart of glass1 (HEG1) directly binds to and recruits Krev interaction trapped protein 1 (KRIT1) to endothelial junctions to form the HEG1-KRIT1 protein complex that establishes and maintains junctional integrity. Genetic inactivation or knockdown of endothelial HEG1 or KRIT1 leads to the upregulation of transcription factors Krüppel-like factors 4 and 2 (KLF4 and KLF2), which are implicated in endothelial vascular homeostasis; however, the effect of acute inhibition of the HEG1-KRIT1 interaction remains incompletely understood. Here, we report a high-throughput screening assay and molecular design of a small-molecule HEG1-KRIT1 inhibitor to uncover acute changes in signaling pathways... More

关键词

HEG1, KLF2, KLF4, KRIT1, endothelial cells