Please use this identifier to cite or link to this item:
Title: Parkin Somatic Mutations Link Melanoma and Parkinson’s Disease
Authors: Qutob, Nouar
Keywords: Melanoma;Parkinson's disease
Issue Date: 2016
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
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
Appears in Collections:Fulltext Publications

Files in This Item:
File Description SizeFormat
Levy-C_2016_PARK2-somatic-mutations-link-melanoma-and-Parkinson’s-disease..pdf1.7 MBAdobe PDFView/Open
Show full item record

Page view(s)

Last Week
Last month
checked on Jun 27, 2024


checked on Jun 27, 2024

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.