Small, N-Terminal Tags Activate Parkin E3 Ubiquitin Ligase Activity by Disrupting Its Autoinhibited Conformation

被引：35

作者：

Burchell, Lynn ^{[1
]}

Chaugule, Viduth K. ^{[1
]}

Walden, Helen ^{[1
]}

机构：

[1] London Res Inst Canc Res UK, Lincolns Inn Fields Labs, Prot Struct & Funct Lab, London, England

来源：

PLOS ONE | 2012年 / 7卷 / 04期

关键词：

RECESSIVE JUVENILE PARKINSONISM; PROTEIN LIGASE; PATHOGENIC MUTATIONS; DISEASE; MITOPHAGY; PINK1; GENE; PHOSPHORYLATION; MITOCHONDRIA; CELLS;

D O I：

10.1371/journal.pone.0034748

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Parkin is an E3 ubiquitin ligase, mutations in which cause Autosomal Recessive Parkinson's Disease. Many studies aimed at understanding Parkin function, regulation and dysfunction are performed using N-terminal epitope tags. We report here that the use of small tags such as FLAG, cMyc and HA, influence the physical stability and activity of Parkin in and out of cells, perturbing the autoinhibited native state of Parkin, resulting in an active-for-autoubiquitination species.

引用

收藏

页数：6

相关论文

共 39 条

[1]

[Anonymous], DRUG DISCOVERY TODAY

[2]

Proteasome inhibition and aggregation in Parkinson's disease: a comparative study in untransfected and transfected cells [J].

Biasini, E ;

Fioriti, L ;

Ceglia, I ;

Invernizzi, R ;

Bertoli, A ;

Chiesa, R ;

Forloni, G .

JOURNAL OF NEUROCHEMISTRY, 2004, 88 (03) :545-553

[3]

Bonifati Vincenzo, 2012, Parkinsonism Relat Disord, V18 Suppl 1, pS4, DOI 10.1016/S1353-8020(11)70004-9

[4]

Autoregulation of Parkin activity through its ubiquitin-like domain [J].

Chaugule, Viduth K. ;

Burchell, Lynn ;

Barber, Kathryn R. ;

Sidhu, Ateesh ;

Leslie, Simon J. ;

Shaw, Gary S. ;

Walden, Helen .

EMBO JOURNAL, 2011, 30 (14) :2853-2867

[5]

Parkin Mediates Apparent E2-Independent Monoubiquitination In Vitro and Contains an Intrinsic Activity That Catalyzes Polyubiquitination [J].

Chew, Katherine C. M. ;

Matsuda, Noriyuki ;

Saisho, Keiko ;

Lim, Grace G. Y. ;

Chai, Chou ;

Tan, Hui-Mei ;

Tanaka, Keiji ;

Lim, Kah-Leong .

PLOS ONE, 2011, 6 (05)

[6]

Identification of sites of ubiquitination in proteins: A Fourier transform ion cyclotron resonance mass spectrometry approach [J].

Cooper, HJ ;

Heath, JK ;

Jaffray, E ;

Hay, RT ;

Lam, TT ;

Marshall, AG .

ANALYTICAL CHEMISTRY, 2004, 76 (23) :6982-6988

[7]

The Role of Parkin in Familial and Sporadic Parkinson's Disease [J].

Dawson, Ted M. ;

Dawson, Valina L. .

MOVEMENT DISORDERS, 2010, 25 (03) :S32-S39

[8]

Ataxin-3 Deubiquitination Is Coupled to Parkin Ubiquitination via E2 Ubiquitin-conjugating Enzyme [J].

Durcan, Thomas M. ;

Kontogiannea, Maria ;

Bedard, Nathalie ;

Wing, Simon S. ;

Fon, Edward A. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (01) :531-541

[9]

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability [J].

Durcan, Thomas M. ;

Kontogiannea, Maria ;

Thorarinsdottir, Thorhildur ;

Fallon, Lara ;

Williams, Aislinn J. ;

Djarmati, Ana ;

Fantaneanu, Tadeu ;

Paulson, Henry L. ;

Fon, Edward A. .

HUMAN MOLECULAR GENETICS, 2011, 20 (01) :141-154

[10]

The cellular protein level of parkin is regulated by its ubiquitin-like domain [J].

Finney, N ;

Walther, F ;

Mantel, PY ;

Stauffer, D ;

Rovelli, G ;

Dev, KK .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (18) :16054-16058

← 1 2 3 4 →