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Parkin-mediated ubiquitination regulates phospholipase C-gamma1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Parkin-mediated ubiquitination regulates phospholipase C-gamma1. / Dehvari, Nodi; Sandebring, Anna; Flores-Morales, Amilcar; Mateos, Laura; Chuan, Yin-Choy; Goldberg, Matthew S; Cookson, Mark R; Cowburn, Richard F; Cedazo-Mínguez, Angel.

I: Journal of Cellular and Molecular Medicine, Bind 13, Nr. 9B, 2008, s. 3061-8.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Dehvari, N, Sandebring, A, Flores-Morales, A, Mateos, L, Chuan, Y-C, Goldberg, MS, Cookson, MR, Cowburn, RF & Cedazo-Mínguez, A 2008, 'Parkin-mediated ubiquitination regulates phospholipase C-gamma1', Journal of Cellular and Molecular Medicine, bind 13, nr. 9B, s. 3061-8. https://doi.org/10.1111/j.1582-4934.2008.00443.x

APA

Dehvari, N., Sandebring, A., Flores-Morales, A., Mateos, L., Chuan, Y-C., Goldberg, M. S., ... Cedazo-Mínguez, A. (2008). Parkin-mediated ubiquitination regulates phospholipase C-gamma1. Journal of Cellular and Molecular Medicine, 13(9B), 3061-8. https://doi.org/10.1111/j.1582-4934.2008.00443.x

Vancouver

Dehvari N, Sandebring A, Flores-Morales A, Mateos L, Chuan Y-C, Goldberg MS o.a. Parkin-mediated ubiquitination regulates phospholipase C-gamma1. Journal of Cellular and Molecular Medicine. 2008;13(9B):3061-8. https://doi.org/10.1111/j.1582-4934.2008.00443.x

Author

Dehvari, Nodi ; Sandebring, Anna ; Flores-Morales, Amilcar ; Mateos, Laura ; Chuan, Yin-Choy ; Goldberg, Matthew S ; Cookson, Mark R ; Cowburn, Richard F ; Cedazo-Mínguez, Angel. / Parkin-mediated ubiquitination regulates phospholipase C-gamma1. I: Journal of Cellular and Molecular Medicine. 2008 ; Bind 13, Nr. 9B. s. 3061-8.

Bibtex

@article{e74cabc03cab11df928f000ea68e967b,
title = "Parkin-mediated ubiquitination regulates phospholipase C-gamma1",
abstract = "Mutations in parkin cause autosomal recessive forms of Parkinson's disease (PD), with an early age of onset and similar pathological phenotype to the idiopathic disease. Parkin has been identified as an E3 ubiquitin ligase that mediates different types of ubiquitination, which has made the search for substrates an intriguing possibility to identify pathological mechanisms linked to PD. In this study, we present PLCgamma1 as a novel substrate for parkin. This association was found in non-transfected human neuroblastoma SH-SY5Y cells as well as in stable cell lines expressing parkin WT and familial mutants R42P and G328E. Analysis of cortical, striatal and nigral human brain homogenates revealed that the interaction between parkin and PLCgamma1 is consistent throughout these regions, suggesting that the interaction is likely to have a physiological relevance for humans. Unlike many of the previously identified substrates, we could also show that the steady-state levels of PLCgamma1 is significantly higher in parkin KO mice and lower in parkin WT human neuroblastoma cells, suggesting that parkin ubiquitination of PLCgamma1 is required for proteasomal degradation. In line with this idea, we show that the ability to ubiquitinate PLCgamma1 in vitro differs significantly between WT and familial mutant parkin. In this study, we demonstrate that parkin interacts with PLCgamma1, affecting PLCgamma1 steady state protein levels in human and murine models with manipulated parkin function and expression levels. This finding could be of relevance for finding novel pathogenic mechanisms leading to PD.",
author = "Nodi Dehvari and Anna Sandebring and Amilcar Flores-Morales and Laura Mateos and Yin-Choy Chuan and Goldberg, {Matthew S} and Cookson, {Mark R} and Cowburn, {Richard F} and Angel Cedazo-M{\'i}nguez",
year = "2008",
doi = "10.1111/j.1582-4934.2008.00443.x",
language = "English",
volume = "13",
pages = "3061--8",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "9B",

}

RIS

TY - JOUR

T1 - Parkin-mediated ubiquitination regulates phospholipase C-gamma1

AU - Dehvari, Nodi

AU - Sandebring, Anna

AU - Flores-Morales, Amilcar

AU - Mateos, Laura

AU - Chuan, Yin-Choy

AU - Goldberg, Matthew S

AU - Cookson, Mark R

AU - Cowburn, Richard F

AU - Cedazo-Mínguez, Angel

PY - 2008

Y1 - 2008

N2 - Mutations in parkin cause autosomal recessive forms of Parkinson's disease (PD), with an early age of onset and similar pathological phenotype to the idiopathic disease. Parkin has been identified as an E3 ubiquitin ligase that mediates different types of ubiquitination, which has made the search for substrates an intriguing possibility to identify pathological mechanisms linked to PD. In this study, we present PLCgamma1 as a novel substrate for parkin. This association was found in non-transfected human neuroblastoma SH-SY5Y cells as well as in stable cell lines expressing parkin WT and familial mutants R42P and G328E. Analysis of cortical, striatal and nigral human brain homogenates revealed that the interaction between parkin and PLCgamma1 is consistent throughout these regions, suggesting that the interaction is likely to have a physiological relevance for humans. Unlike many of the previously identified substrates, we could also show that the steady-state levels of PLCgamma1 is significantly higher in parkin KO mice and lower in parkin WT human neuroblastoma cells, suggesting that parkin ubiquitination of PLCgamma1 is required for proteasomal degradation. In line with this idea, we show that the ability to ubiquitinate PLCgamma1 in vitro differs significantly between WT and familial mutant parkin. In this study, we demonstrate that parkin interacts with PLCgamma1, affecting PLCgamma1 steady state protein levels in human and murine models with manipulated parkin function and expression levels. This finding could be of relevance for finding novel pathogenic mechanisms leading to PD.

AB - Mutations in parkin cause autosomal recessive forms of Parkinson's disease (PD), with an early age of onset and similar pathological phenotype to the idiopathic disease. Parkin has been identified as an E3 ubiquitin ligase that mediates different types of ubiquitination, which has made the search for substrates an intriguing possibility to identify pathological mechanisms linked to PD. In this study, we present PLCgamma1 as a novel substrate for parkin. This association was found in non-transfected human neuroblastoma SH-SY5Y cells as well as in stable cell lines expressing parkin WT and familial mutants R42P and G328E. Analysis of cortical, striatal and nigral human brain homogenates revealed that the interaction between parkin and PLCgamma1 is consistent throughout these regions, suggesting that the interaction is likely to have a physiological relevance for humans. Unlike many of the previously identified substrates, we could also show that the steady-state levels of PLCgamma1 is significantly higher in parkin KO mice and lower in parkin WT human neuroblastoma cells, suggesting that parkin ubiquitination of PLCgamma1 is required for proteasomal degradation. In line with this idea, we show that the ability to ubiquitinate PLCgamma1 in vitro differs significantly between WT and familial mutant parkin. In this study, we demonstrate that parkin interacts with PLCgamma1, affecting PLCgamma1 steady state protein levels in human and murine models with manipulated parkin function and expression levels. This finding could be of relevance for finding novel pathogenic mechanisms leading to PD.

U2 - 10.1111/j.1582-4934.2008.00443.x

DO - 10.1111/j.1582-4934.2008.00443.x

M3 - Journal article

C2 - 18671761

VL - 13

SP - 3061

EP - 3068

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 9B

ER -

ID: 18947135