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Fig. 3 | Cell & Bioscience

Fig. 3

From: Overview of multifunctional cysteinyl cathepsins in atherosclerosis-based cardiovascular disease: from insights into molecular functions to clinical implications

Fig. 3

A molecular model of CTSK-mediated Notch-1 activation in endothelial cells. The notch1 receptor is synthesized in precursor forms that are cleaved by the enzymes at the following three sites. S1, by furin-like convertase to generate the mature receptor; S2, by the metalloproteinase tumor necrosis factor α-converting enzyme (TACE, also known as ADAM17); and S3, by γ-secretase or cathepsin K (CTSK) to generate the Notch intracellular domain (NICD). VEGF stimulates CTSK expression by VEGFR-PI3K/Akt signaling activation in endothelial cells. Following CTSK-mediated proteolytic processing, the NICD moves into the nucleus, which triggers downstream angiogenic factor transcription for the modulation of EC migration, microtubule formation, proliferation, and apoptosis/death. The NICD is also targeted to the endosome for degradation. Akt: protein kinase B/Akt; Flt-1: fms-like tyrosine kinase 1; Hes-1: hairy enhancer of split homolog-1; Hey-1: Hes-related repressor protein-1; MAM: master mind; PI3K: phosphatidylinositol 3-kinase; VEGF: vascular endothelial growth factor; VEGFR: VEGF receptor

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