Diverse effects of pathogenic mutations of Parkin that catalyzes multiple monoubiquitylation in vitro

doi:10.1074/jbc.M510393200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on February 10, 2006

This Article

	Full Text (Accepted Manuscript)
	Supplemental Data
	All Versions of this Article: 281/6/3204 most recent M510393200v1
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Request Permissions

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Matsuda, N.
	Articles by Tanaka, K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Matsuda, N.
	Articles by Tanaka, K.

Social Bookmarking

	What's this?

Papers In Press, published online ahead of print December 8, 2005
J. Biol. Chem, 10.1074/jbc.M510393200
Submitted on September 21, 2005
Revised on November 29, 2005
Accepted on December 8, 2005

Diverse effects of pathogenic mutations of Parkin that catalyzes multiple monoubiquitylation in vitro

Noriyuki Matsuda, Toshiaki Kitami, Toshiaki Suzuki, Yoshikuni Mizuno, Nobutaka Hattori, and Keiji Tanaka

Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613

Corresponding Author: tanakak{at}rinshoken.or.jp

Mutational dysfunction of PARKIN gene, which encodes a double RING finger protein and has ubiquitin ligase E3 activity, is the major cause of autosomal recessive juvenile Parkinsonism. Although many studies explored the functions of Parkin, its biochemical character is poorly understood. To address this issue, we established an E3 assay system using maltose-binding protein-fused Parkin purified from Escherichia coli. Using this recombinant Parkin, we found that not the front but the rear RING finger motif is responsible for the E3 activity of Parkin and it catalyzes multiple monoubiquitylation. Intriguingly, for autosomal recessive juvenile Parkinsonism-causing mutations of Parkin, whereas there was loss of E3 activity in the rear RING domain, other pathogenic mutants still exhibited E3 activity equivalent to that of the wild-type Parkin. The evidence presented allows us to reconsider the function of Parkin-catalyzed ubiquitylation and to conclude that autosomal recessive juvenile Parkinsonism is not solely attributable to catalytic impairment of Parkin’s E3 activity.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

T. D. Helton, T. Otsuka, M.-C. Lee, Y. Mu, and M. D. Ehlers
Pruning and loss of excitatory synapses by the parkin ubiquitin ligase
PNAS, December 9, 2008; 105(49): 19492 - 19497.
[Abstract] [Full Text] [PDF]

C. Klein and M. G. Schlossmacher
Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder
Neurology, November 27, 2007; 69(22): 2093 - 2104.
[Abstract] [Full Text] [PDF]

M. R. Cookson, W. Dauer, T. Dawson, E. A. Fon, M. Guo, and J. Shen
The Roles of Kinases in Familial Parkinson's Disease
J. Neurosci., October 31, 2007; 27(44): 11865 - 11868.
[Abstract] [Full Text] [PDF]

J. A. Olzmann, L. Li, M. V. Chudaev, J. Chen, F. A. Perez, R. D. Palmiter, and L.-S. Chin
Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6
J. Cell Biol., September 7, 2007; 178(6): 1025 - 1038.
[Abstract] [Full Text] [PDF]

M. Joch, A. R. Ase, C. X.-Q. Chen, P. A. MacDonald, M. Kontogiannea, A. T. Corera, A. Brice, P. Seguela, and E. A. Fon
Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels
Mol. Biol. Cell, August 1, 2007; 18(8): 3105 - 3118.
[Abstract] [Full Text] [PDF]

J. J. Yi and M. D. Ehlers
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function
Pharmacol. Rev., March 1, 2007; 59(1): 14 - 39.
[Abstract] [Full Text] [PDF]

I. H. Henn, L. Bouman, J. S. Schlehe, A. Schlierf, J. E. Schramm, E. Wegener, K. Nakaso, C. Culmsee, B. Berninger, D. Krappmann, et al.
Parkin Mediates Neuroprotection through Activation of I{kappa}B Kinase/Nuclear Factor-{kappa}B Signaling
J. Neurosci., February 21, 2007; 27(8): 1868 - 1878.
[Abstract] [Full Text] [PDF]

C. Hampe, H. Ardila-Osorio, M. Fournier, A. Brice, and O. Corti
Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity
Hum. Mol. Genet., July 1, 2006; 15(13): 2059 - 2075.
[Abstract] [Full Text] [PDF]