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ADAM10 activates NOTCH1. 31 / 33
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"Inhibition of ADAM10 abrogates NOTCH1 signaling in human T-ALL."
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"It was also shown that NOTCH1 can be activated by ADAM10 (A Disintegrin and metalloproteinase domain-containing protein 10), a sheddase with α -secretase activity, and promoted migration and invasion of the A549 lung adenocarcinoma cells [ xref ]."
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"Interestingly, Tspan15 negatively regulates Notch activity, probably indirectly by competing with Tspan14 for ADAM10 binding, whereas Tspan14 is important for ADAM10-regulated activation of Notch1 (Dornier et al., 2012; Jouannet et al., 2016)."
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"This association aligns with the findings of Caolo et al. (2019), who demonstrated that in endothelial cells, mechanical activation of PIEZO1 induces calcium influx, leading to ADAM10-dependent NOTCH1 cleavage and activation, ultimately driving the expression of Notch target genes and maintaining vascular homeostasis [ xref ]."
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"Notch1 activation is mediated by ADAM10, a molecular scissor that separates the target protein from its substrates in the cell membrane."
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"After activation, Notch can be cleaved to its intracellular domain (NICD) by ADAM10, TACE and gamma-secretase, allowing the NICD to become capable of target gene activation [XREF_BIBR]."
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"As shown in XREF_FIG, overexpression of ADAM10 elicited stronger fluorescent signals of Notch1 IC and Notch3 IC in the nucleus, reflecting increased nuclear translocation of these molecules, whereas Notch1 IC and Notch3 IC signals were evenly distributed in the vector transduced cells."
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"Adam10, which cleaves the Notch ligands at the S2 site and produces the NICD to activate Notch signalling [15], had the same expression trend with Notch1 and Notch2."
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"ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development"
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"It was also shown that NOTCH1 can be activated by ADAM10 (A Disintegrin and metalloproteinase domain containing protein 10), a sheddase with alpha-secretase activity, and promoted migration and invasion of the A549 lung adenocarcinoma cells [XREF_BIBR]."
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"Inhibition of ADAM10 expression can also inhibit Notch1 signal transduction and make drug-resistant cells re-sensitive to enzalamide [35]."
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"ADAM10 is essential for early embryonic development and important in the hematopoietic system, which is largely attributed to the cleavage and activation of NOTCH1 by ADAM10 [ xref , xref ]."
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"Recombinant ADAMTS1 reversed ADAM10-induced muscle cell atrophy by suppressing NOTCH1 activation and downregulating its target gene."
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"ADAM10 sheddase, which mediates the effect of PIEZO1 on NOTCH1 , cleaves CDH5 ."
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"Activated PIEZO1 mediates the inward flow of Ca to activate the metalloproteinase ADAM10 (Ca -dependent transmembrane abscission enzyme), which participates in the Notch1 pathway as a regulator of S2 cleavage and induces cleavage of the Notch1 S2 site, followed by the γ-secretase that prompts the cleavage of the Notch1 S3 site which leads to the release of N1IDC."
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"ADAM10 mediated Notch1 cleavage and shedding in T-cells controls T-cell development [XREF_BIBR], and also contributes to oncogenic Notch signaling by shedding Notch1 mutants in T-cell acute lymphoblastic leukemia (T-ALL) [XREF_BIBR]."
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"Recombinant ADAMTS1 inhibits ADAM10-mediated NOTCH1 activation."
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"58 Loss of ADAM10 function was found to impair the cleavage of Notch1 in ECs and inhibit its intracellular Notch signaling transduction."
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"To evaluate if Notch-1 activation induced by RLX in H9c2 and NIH3T3 cells was mediated by ADAM10 via PI3K/Akt signaling, both cell types were treated with RLX in the presence or absence of WT and TCN,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"While also expressed in immune cells, TSPAN14 has an intestinal epithelial role as a positive regulator of ligand induced ADAM10 mediated Notch1 activation."
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"These results indicate that knockdown of ADAM10 by siRNA in TNBC cells inhibits cell proliferation by regulating Notch1, HES1 and c-Myc, and induces cell-cycle arrest by regulating Cyclin D3 and p21 Waf1 and Cip1."
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"Most recently, two groups using ADAM10 -/- MEFs concluded that ADAM10 mediates ligand dependent Notch1 cleavage, whereas other proteases regulate ligand independent cleavage."
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"ADAM10 is essential for early embryonic development and important in the hematopoietic system, which is largely attributed to the cleavage and activation of NOTCH1 by ADAM10 [28, 29]."
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"In human patients with non small cell lung cancer, ADAM10 overexpression activated the Notch1 signaling pathway, leading to increased cell migration and invasion [XREF_BIBR]."
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"For instance, miR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10 mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma [XREF_BIBR]."
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"In this regard, another study related to the Notch1 signaling pathway showed that miR-140–5p, as a tumor suppressor, can inhibit the ADAM10-mediated Notch1 signaling pathway and thus suppress tumor migration and invasion in hypopharyngeal squamous cell carcinoma (HSCC) [76]."
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"Therefore, IMD could inhibit ADAM10 protein expression via its CRLR and RAMP receptor and the PI3K and Akt signaling pathway, thereby inhibiting the activation of Notch1."
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"Interestingly, a recent report suggested that Notch1 signaling pathway activated by ADAM10 shedding played non small cell lung cancer in the migration and invasion of non small cell lung cancer (Guo e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Hence, we focused on the role of ADAM10 mediated Notch1 signaling shedding and activation in HSCC.To date, the dysregulated Notch1 signaling pathway has been observed to mediate tumor migration and in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, further studies are needed to unequivocally establish if ADAM10 mediates the cleavage of both NOTCH1 and NOTCH3 during early retinal neurogenesis."
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"Similarly, expression of exogenous Adam10 or Adam17 in mouse embryonic fibroblasts (MEFs) derived from Adam10 and Adam17 knockout animals, effectively increased activation of NOTCH1 signaling upon expression of activated forms of NOTCH1 in these cells (XREF_FIG)."
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