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Protein Complex Linked To Parkinson Disease

Date:
March 4, 2009
Source:
Journal of Clinical Investigation
Summary:
Mutations in the genes PINK1, PARKIN, and DJ-1 have each been linked to early-onset inherited forms of Parkinson disease. However, the functional relationship between the proteins generated by these genes and how the mutations lead to Parkinson disease are not well understood.

Mutations in the genes PINK1, PARKIN, and DJ-1 have each been linked to early-onset inherited forms of Parkinson disease. However, the functional relationship between the proteins generated by these genes and how the mutations lead to Parkinson disease are not well understood.

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Now, Zhuohua Zhang and colleagues, at the Burnham Institute for Medical Research, La Jolla, have determined that the proteins generated by these genes form a complex in neuroblastoma cells and human brain lysates. Further analysis indicated the function of this complex and how this is impaired by mutant forms of the proteins associated with Parkinson disease.

The research is published Feb. 23, 2009, in the Journal of Clinical Investigation.

In the study, the Parkin/PINK1/DJ-1 complex was shown to control the degradation of certain proteins (including Parkin itself) in neuroblastoma cells and human brain lysates. If the complex contained the mutant forms of either PINK1 or Parkin associated with Parkinson disease, its ability to degrade proteins was dramatically reduced.

The authors therefore suggest that the proteins generated by the three Parkinson disease–associated genes PINK1, PARKIN, and DJ-1 function in a common pathway and that dysfunction in this pathway might underlie the development of Parkinson disease in individuals with mutations in these genes.

In an accompanying commentary, Han Li and Ming Guo, at the David Geffen School of Medicine and Molecular Biology Institute, Los Angeles, put these data in context with other studies indicating additional roles for PINK1 and PARKIN.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal References:

  1. Xiong et al. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI37617
  2. Guo et al. Protein degradation in Parkinson disease revisited: it's complex. Journal of Clinical Investigation, 2009; [link]

Cite This Page:

Journal of Clinical Investigation. "Protein Complex Linked To Parkinson Disease." ScienceDaily. ScienceDaily, 4 March 2009. <www.sciencedaily.com/releases/2009/02/090224004510.htm>.
Journal of Clinical Investigation. (2009, March 4). Protein Complex Linked To Parkinson Disease. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2009/02/090224004510.htm
Journal of Clinical Investigation. "Protein Complex Linked To Parkinson Disease." ScienceDaily. www.sciencedaily.com/releases/2009/02/090224004510.htm (accessed October 26, 2014).

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