IndraLab

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NEDD4L activates KCNH2. 5 / 5
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"HERG1 modulation by Nedd4-2 leads to the specific reduction of functional channel levels at the cell surface and the subsequent decrease of hERG1 mediated currents.Guinea pigs were obtained from the g[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"To confirm that the presence of both minor alleles in AS-iPSC-CMs can reduce MTMR4 dephosphorylation activity, thus blunting the proteasomal degradation of KCNQ1 and hERG mediated by Nedd4L, we generated MTMR4 corrected AS-iPSCs (AS-MTMR4Cor-iPSCs), using CRISPR and Cas9 technology."

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"We have previously shown that the E3 ubiquitin (Ub) ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) targets the PY motif of hERG channels to initiate channel degradation."

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"Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2."

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"Rab4 interferes with Nedd4-2 degradation, resulting in an increased expression level of Nedd4-2, which targets hERG."