Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation

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Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. / Pao, Kuan Chuan; Stanley, Mathew; Han, Cong; Lai, Yu Chiang; Murphy, Paul; Balk, Kristin; Wood, Nicola T.; Corti, Olga; Corvol, Jean Christophe; Muqit, Miratul M.K.; Virdee, Satpal.

In: Nature Chemical Biology, Vol. 12, No. 5, 07.03.2016, p. 324-331.

Research output: Contribution to journalArticlepeer-review

Harvard

Pao, KC, Stanley, M, Han, C, Lai, YC, Murphy, P, Balk, K, Wood, NT, Corti, O, Corvol, JC, Muqit, MMK & Virdee, S 2016, 'Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation', Nature Chemical Biology, vol. 12, no. 5, pp. 324-331. https://doi.org/10.1038/nchembio.2045

APA

Pao, K. C., Stanley, M., Han, C., Lai, Y. C., Murphy, P., Balk, K., Wood, N. T., Corti, O., Corvol, J. C., Muqit, M. M. K., & Virdee, S. (2016). Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. Nature Chemical Biology, 12(5), 324-331. https://doi.org/10.1038/nchembio.2045

Vancouver

Author

Pao, Kuan Chuan ; Stanley, Mathew ; Han, Cong ; Lai, Yu Chiang ; Murphy, Paul ; Balk, Kristin ; Wood, Nicola T. ; Corti, Olga ; Corvol, Jean Christophe ; Muqit, Miratul M.K. ; Virdee, Satpal. / Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. In: Nature Chemical Biology. 2016 ; Vol. 12, No. 5. pp. 324-331.

Bibtex

@article{f26226e308b846c1959cf78d8b6485b8,
title = "Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation",
abstract = "E3 ligases represent an important class of enzymes, yet there are currently no chemical probes for profiling their activity. We develop a new class of activity-based probe by re-engineering a ubiquitin-charged E2 conjugating enzyme and demonstrate the utility of these probes by profiling the transthiolation activity of the RING-in-between-RING (RBR) E3 ligase parkin in vitro and in cellular extracts. Our study provides valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in parkin activation. We also profile parkin mutations associated with patients with Parkinson's disease and demonstrate that they mediate their effect largely by altering transthiolation activity. Furthermore, our probes enable direct and quantitative measurement of endogenous parkin activity, revealing that endogenous parkin is activated in neuronal cell lines (≥75%) in response to mitochondrial depolarization. This new technology also holds promise as a novel biomarker of PINK1-parkin signaling, as demonstrated by its compatibility with samples derived from individuals with Parkinson's disease.",
author = "Pao, {Kuan Chuan} and Mathew Stanley and Cong Han and Lai, {Yu Chiang} and Paul Murphy and Kristin Balk and Wood, {Nicola T.} and Olga Corti and Corvol, {Jean Christophe} and Muqit, {Miratul M.K.} and Satpal Virdee",
year = "2016",
month = mar,
day = "7",
doi = "10.1038/nchembio.2045",
language = "English",
volume = "12",
pages = "324--331",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation

AU - Pao, Kuan Chuan

AU - Stanley, Mathew

AU - Han, Cong

AU - Lai, Yu Chiang

AU - Murphy, Paul

AU - Balk, Kristin

AU - Wood, Nicola T.

AU - Corti, Olga

AU - Corvol, Jean Christophe

AU - Muqit, Miratul M.K.

AU - Virdee, Satpal

PY - 2016/3/7

Y1 - 2016/3/7

N2 - E3 ligases represent an important class of enzymes, yet there are currently no chemical probes for profiling their activity. We develop a new class of activity-based probe by re-engineering a ubiquitin-charged E2 conjugating enzyme and demonstrate the utility of these probes by profiling the transthiolation activity of the RING-in-between-RING (RBR) E3 ligase parkin in vitro and in cellular extracts. Our study provides valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in parkin activation. We also profile parkin mutations associated with patients with Parkinson's disease and demonstrate that they mediate their effect largely by altering transthiolation activity. Furthermore, our probes enable direct and quantitative measurement of endogenous parkin activity, revealing that endogenous parkin is activated in neuronal cell lines (≥75%) in response to mitochondrial depolarization. This new technology also holds promise as a novel biomarker of PINK1-parkin signaling, as demonstrated by its compatibility with samples derived from individuals with Parkinson's disease.

AB - E3 ligases represent an important class of enzymes, yet there are currently no chemical probes for profiling their activity. We develop a new class of activity-based probe by re-engineering a ubiquitin-charged E2 conjugating enzyme and demonstrate the utility of these probes by profiling the transthiolation activity of the RING-in-between-RING (RBR) E3 ligase parkin in vitro and in cellular extracts. Our study provides valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in parkin activation. We also profile parkin mutations associated with patients with Parkinson's disease and demonstrate that they mediate their effect largely by altering transthiolation activity. Furthermore, our probes enable direct and quantitative measurement of endogenous parkin activity, revealing that endogenous parkin is activated in neuronal cell lines (≥75%) in response to mitochondrial depolarization. This new technology also holds promise as a novel biomarker of PINK1-parkin signaling, as demonstrated by its compatibility with samples derived from individuals with Parkinson's disease.

UR - http://www.scopus.com/inward/record.url?scp=84959192267&partnerID=8YFLogxK

U2 - 10.1038/nchembio.2045

DO - 10.1038/nchembio.2045

M3 - Article

C2 - 26928937

AN - SCOPUS:84959192267

VL - 12

SP - 324

EP - 331

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 5

ER -