HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 6, 3204-3209, February 10, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/6/3204    most recent M510393200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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?

Diverse Effects of Pathogenic Mutations of Parkin That Catalyze Multiple Monoubiquitylation in Vitro^*

Noriyuki Matsuda, Toshiaki Kitami, Toshiaki Suzuki, Yoshikuni Mizuno, Nobutaka Hattori, and Keiji Tanaka¹

From the Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 and the Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

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 the E3 activity of Parkin.

Received for publication, September 21, 2005 , and in revised form, November 29, 2005.

^* This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to K. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1 and Fig. 1.

¹ To whom correspondence should be addressed. Tel. and Fax: +81-3-3823-2237; E-mail: tanakak{at}rinshoken.or.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    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]