IndraLab

"The hERG (human ether-a-go-go-related gene, Kv11.1, KCNH2) K channel, responsible for the IKr (rapid) current component in cardiac myocytes and mutated in type 2 long-QT syndrome, was reported to interact with NDFIP1 and NDFIP2 and was ubiquitinated by Nedd4-2 [55]."

"UbiNet 2.0"

"Nedd4-2 ubiquitinates the epithelial sodium channel ENaC [XREF_BIBR], the chloride channel ClC-5, voltage gated potassium and the cardiac potassium channel hERG1 [XREF_BIBR]."

"These two complementary methods enabled us to confirm that hERG1 was most likely directly ubiquitylated by Nedd4-2, since Nedd4-2 co-expression robustly increased the ubiquitylation of the channel."

"As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect."

"Moreover, they also suggest that, at least in expression systems, the formation of a complex ubiquitin ligase-target protein is not inevitably followed by ubiquitylation of the protein.The present stu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Further experiments will be needed to confirm these results.In addition, hERG1 channels ubiquitylated by Nedd4-2 appear to be targeted to the proteasomal rather than to the lysosomal pathway, although[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Therefore, we proposed that increased Nedd4-2 activity in pCH enhanced ubiquitylation of Kv11.1 and accelerated its degradation, leading to I reduction and consequent arrhythmogenesis."

"As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface."

"In conclusion, the results of the present work indicate that ubiquitylation of hERG1 by the ubiquitin ligase Nedd4-2 is a potentially constitutive physiological mechanism for the regulation of hERG1 c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"