Please use this identifier to cite or link to this item:
http://hdl.handle.net/20.500.11889/4176
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Qutob, Nouar | - |
dc.date.accessioned | 2017-01-30T09:36:13Z | - |
dc.date.available | 2017-01-30T09:36:13Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11889/4176 | - |
dc.description | Authors include:Lotan Levin, Shani Srour, Jared Gartner, Oxana Kapitansky, Nouar Qutob, Shani Dror , Tamar Golan , Roy Dayan , Ronen Brener , Tamar Ziv, Mehdi Khaled , Ora Schueler-Furman, Yardena Samuels , Carmit Levy | en_US |
dc.description.abstract | Epidemiological studies suggest a direct link between melanoma and Parkinson’s disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson’s disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases | en_US |
dc.language.iso | en_US | en_US |
dc.subject | Melanoma | en_US |
dc.subject | Parkinson's disease | en_US |
dc.title | Parkin Somatic Mutations Link Melanoma and Parkinson’s Disease | en_US |
dc.type | Article | en_US |
newfileds.department | Science | en_US |
newfileds.item-access-type | open_access | en_US |
newfileds.thesis-prog | none | en_US |
newfileds.general-subject | none | en_US |
item.languageiso639-1 | other | - |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
Appears in Collections: | Fulltext Publications |
Files in This Item:
File | Description | Size | Format | |
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Levy-C_2016_PARK2-somatic-mutations-link-melanoma-and-Parkinson’s-disease..pdf | 1.7 MB | Adobe PDF | View/Open |
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