IndraLab

Statements


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sparser
"CLEC16A is described to stabilize the complex it forms with NRDP1 and USP8 by adding non-degradative ubiquitin conjugates to NRDP1 (Pearson et al. xref )."

reach
"First, Nrdp1 overexpression leads to increased protein ubiquitylation and suppressed interaction between Nrdp1 and USP8 (due to increased USP8 degradation)."

reach
"Moreover, mutation of the CLEC16A internal IDR reduced binding between RNF41 and USP8."

reach
"Nrdp1 interacts with two upstream regulators of mitophagy: Clec16a and the deubiquitinase (DUB) enzyme USP8 (5,25)."

reach
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 (Fig. 4E)."

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sparser
"The crystal structure of the rhodanese domain of USP8 in complex with Nrdp1 was solved and revealed that the USP8-Nrdp1 interaction appeared to be dominated by salt bridges [ xref ]."

reach
"However, palmitate treatment did not additively reduce Nrdp1-USP8 binding in shClec16a-treated Min6 β-cells (Fig. 6A), suggesting that palmitate acts to destabilize the Nrdp1-USP8 complex through effects on the Clec16a pathway."

reach
"Utilizing the sensitive proximity ligation assay technique to detect interaction of the mitophagy regulators NRDP1 and USP8, we are able to specifically quantify formation of essential mitophagy complexes in situ."

sparser
"Specifically, MAGEL2 interacts with TRIM27 and USP7 to modify the ubiquitination and stability of WASH1 [ xref ], and interacts with RNF41 and USP8 to modify the ubiquitination and stability of the ESCRT-0 (Endosomal Sorting Complexes Required for Transport) complex [ xref ]."

reach
"Nrdp1 binds and opposes USP8 action on cytokine receptor signaling (42), and Clec16a could function through Nrdp1 to counter USP8 effects on Parkin."

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reach
"Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand stimulated epidermal growth factor receptor down-regulation."

sparser
"Lastly, to ambiguously demonstrate the interactions between Nrdp1 and USP8 and between USP8 and HIF-1α in OGD-treated neurons, we performed co-immunoprecipitation experiments."

sparser
"The Clec16a protein encodes an E3 ubiquitin ligase, and the complex of this factor with Nrdp1 and Usp8 can promote the fusion of mitophagosomes and lysosomes."

sparser
"Utilizing the sensitive proximity ligation assay technique to detect interaction of the mitophagy regulators NRDP1 and USP8, we are able to specifically quantify formation of essential mitophagy complexes in situ."

reach
"Most likely, CLEC16A mainly contributes to mitochondrial health during brain development by promoting PINK/PARKIN-dependent mitophagy via the well-established CLEC16A–NRDP1USP8 complex (Pearson et al. 2018)."

sparser
"The biological significance of the USP8-Nrdp1 interaction is at least partially due to its effect on EGFR regulation."

reach
"The CLEC16A‐NRDP1USP8 complex regulates PARKIN expression and plays a role in autophagosome trafficking to lysosome 58 ."

sparser
"There was evidence that Magel2 was involved in the leptin-POMC of the hypothalamus to maintain the energy balance of the body.[ xref ]Wijesuriya et al have found that MAGEL2 and Necdin connected leptin receptor (LepR) to the USP8-RNF41 ubiquitin complex through the LepR adapter protein, IRS4."

sparser
"Also, RNF41 can interact with the deubiquitylating enzyme USP8 (also called UBPy), which is required for maintenance of ESCRT-0 stability and endosomal sorting of ErbB3 and EGFR ( xref ; xref )."

sparser
"To assess the role of Clec16a-mediated ubiquitination on formation of the β-cell mitophagy complex, we utilized a proximity ligation assay (PLA) to visualize Nrdp1-USP8 association in situ after lenalidomide treatment ( xref )."

sparser
"Lenalidomide impaired Nrdp1-USP8 interaction in Min6 β-cells ( xref ), suggesting that Clec16a-mediated ubiquitination maintains the Clec16a-Nrdp1-USP8 complex as well as β-cell function."

sparser
"To determine whether the combination of reduced Clec16a expression and/or glucolipotoxicity impairs the upstream mitophagy complex, we assessed Nrdp1-USP8 interaction by PLA."

sparser
"As expected, Clec16a- specific shRNA reduced Nrdp1-USP8 binding in situ ( xref )."

sparser
"Nrdp1-USP8 binding was also decreased after palmitate treatment, indicating that glucolipotoxicity destabilizes upstream mitophagy regulators ( xref )."

sparser
"However, palmitate treatment did not additively reduce Nrdp1-USP8 binding in shClec16a-treated Min6 β-cells ( xref ), suggesting that palmitate acts to destabilize the Nrdp1-USP8 complex through effects on the Clec16a pathway."

sparser
"Similarly, glucolipotoxicity decreased Nrdp1-USP8 interaction in primary human β-cells ( xref )."

sparser
"We next determined the role of ubiquitination and Clec16a in stabilization of Nrdp1-USP8 binding utilizing WT and mutant ubiquitin."

sparser
"Indeed, we found that the interaction of NRDP1 and USP8 was decreased following a 48 h exposure to palmitate and high glucose in both beta cell lines as well as primary human beta cells by PLA ( xref and reference xref )."

sparser
"While Clec16a enhanced Nrdp1-USP8 complex assembly, addition of the ubiquitin KO mutant reduced Nrdp1 levels as well as Nrdp1 interaction with both Clec16a and USP8 ( xref )."

sparser
"Apart from a direct effect on gene expression, Dex may influence BRUCE through the recently described Usp8-Nrdp1 system [17,18] ."

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sparser
"Importantly, Clec16a overexpression in palmitate-treated cells raised Nrdp1 levels, Nrdp1 ubiquitination, and Nrdp1-USP8 binding back to baseline levels (BSA alone) ( xref )."

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reach
"USP8 interactions with Nrdp1 and BRUCE."

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sparser
"MAGEL2 links LepR to the USP8-RNF41 ubiquitination complex, while ablation of MAGEL2 suppresses RNF41 stabilization and prevents the MAGEL2 -related increase of cell surface LepR [ xref ]."

No evidence text available

No evidence text available

sparser
"Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand-stimulated epidermal growth factor receptor down-regulation."

reach
"Also, RNF41 can interact with the deubiquitylating enzyme USP8 (also called UBPy), which is required for maintenance of ESCRT-0 stability and endosomal sorting of ErbB3 and EGFR."

reach
"Recently, USP8, Nrdp1 as an E3 ligase, and Clec16a form a complex that has been proposed to maintain mitochondrial quality in β-cell mitophagy ( Pearson et al., 2018 )."