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|Title:||Parkin Somatic Mutations Link Melanoma and Parkinson’s Disease|
|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|
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