Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.
Identifieur interne : 000217 ( PubMed/Corpus ); précédent : 000216; suivant : 000218Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.
Auteurs : 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 LevySource :
- Journal of genetics and genomics = Yi chuan xue bao [ 1673-8527 ] ; 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.
DOI: 10.1016/j.jgg.2016.05.005
PubMed: 27297116
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.</title><author><name sortKey="Levin, Lotan" sort="Levin, Lotan" uniqKey="Levin L" first="Lotan" last="Levin">Lotan Levin</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Srour, Shani" sort="Srour, Shani" uniqKey="Srour S" first="Shani" last="Srour">Shani Srour</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Gartner, Jared" sort="Gartner, Jared" uniqKey="Gartner J" first="Jared" last="Gartner">Jared Gartner</name><affiliation><nlm:affiliation>Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kapitansky, Oxana" sort="Kapitansky, Oxana" uniqKey="Kapitansky O" first="Oxana" last="Kapitansky">Oxana Kapitansky</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Qutob, Nouar" sort="Qutob, Nouar" uniqKey="Qutob N" first="Nouar" last="Qutob">Nouar Qutob</name><affiliation><nlm:affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Dror, Shani" sort="Dror, Shani" uniqKey="Dror S" first="Shani" last="Dror">Shani Dror</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Golan, Tamar" sort="Golan, Tamar" uniqKey="Golan T" first="Tamar" last="Golan">Tamar Golan</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Dayan, Roy" sort="Dayan, Roy" uniqKey="Dayan R" first="Roy" last="Dayan">Roy Dayan</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Brener, Ronen" sort="Brener, Ronen" uniqKey="Brener R" first="Ronen" last="Brener">Ronen Brener</name><affiliation><nlm:affiliation>Oncology Institute, Edith Wolfson Medical Center, Holon 5822012, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Ziv, Tamar" sort="Ziv, Tamar" uniqKey="Ziv T" first="Tamar" last="Ziv">Tamar Ziv</name><affiliation><nlm:affiliation>Technion Smoler Proteomics Center, Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Khaled, Mehdi" sort="Khaled, Mehdi" uniqKey="Khaled M" first="Mehdi" last="Khaled">Mehdi Khaled</name><affiliation><nlm:affiliation>Institut Gustave Roussy, INSERM U753, Villejuif 94805, France.</nlm:affiliation></affiliation></author><author><name sortKey="Schueler Furman, Ora" sort="Schueler Furman, Ora" uniqKey="Schueler Furman O" first="Ora" last="Schueler-Furman">Ora Schueler-Furman</name><affiliation><nlm:affiliation>Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Samuels, Yardena" sort="Samuels, Yardena" uniqKey="Samuels Y" first="Yardena" last="Samuels">Yardena Samuels</name><affiliation><nlm:affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Levy, Carmit" sort="Levy, Carmit" uniqKey="Levy C" first="Carmit" last="Levy">Carmit Levy</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: carmitlevy@post.tau.ac.il.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27297116</idno><idno type="pmid">27297116</idno><idno type="doi">10.1016/j.jgg.2016.05.005</idno><idno type="wicri:Area/PubMed/Corpus">000217</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000217</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.</title><author><name sortKey="Levin, Lotan" sort="Levin, Lotan" uniqKey="Levin L" first="Lotan" last="Levin">Lotan Levin</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Srour, Shani" sort="Srour, Shani" uniqKey="Srour S" first="Shani" last="Srour">Shani Srour</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Gartner, Jared" sort="Gartner, Jared" uniqKey="Gartner J" first="Jared" last="Gartner">Jared Gartner</name><affiliation><nlm:affiliation>Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kapitansky, Oxana" sort="Kapitansky, Oxana" uniqKey="Kapitansky O" first="Oxana" last="Kapitansky">Oxana Kapitansky</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Qutob, Nouar" sort="Qutob, Nouar" uniqKey="Qutob N" first="Nouar" last="Qutob">Nouar Qutob</name><affiliation><nlm:affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Dror, Shani" sort="Dror, Shani" uniqKey="Dror S" first="Shani" last="Dror">Shani Dror</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Golan, Tamar" sort="Golan, Tamar" uniqKey="Golan T" first="Tamar" last="Golan">Tamar Golan</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Dayan, Roy" sort="Dayan, Roy" uniqKey="Dayan R" first="Roy" last="Dayan">Roy Dayan</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Brener, Ronen" sort="Brener, Ronen" uniqKey="Brener R" first="Ronen" last="Brener">Ronen Brener</name><affiliation><nlm:affiliation>Oncology Institute, Edith Wolfson Medical Center, Holon 5822012, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Ziv, Tamar" sort="Ziv, Tamar" uniqKey="Ziv T" first="Tamar" last="Ziv">Tamar Ziv</name><affiliation><nlm:affiliation>Technion Smoler Proteomics Center, Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Khaled, Mehdi" sort="Khaled, Mehdi" uniqKey="Khaled M" first="Mehdi" last="Khaled">Mehdi Khaled</name><affiliation><nlm:affiliation>Institut Gustave Roussy, INSERM U753, Villejuif 94805, France.</nlm:affiliation></affiliation></author><author><name sortKey="Schueler Furman, Ora" sort="Schueler Furman, Ora" uniqKey="Schueler Furman O" first="Ora" last="Schueler-Furman">Ora Schueler-Furman</name><affiliation><nlm:affiliation>Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Samuels, Yardena" sort="Samuels, Yardena" uniqKey="Samuels Y" first="Yardena" last="Samuels">Yardena Samuels</name><affiliation><nlm:affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</nlm:affiliation></affiliation></author><author><name sortKey="Levy, Carmit" sort="Levy, Carmit" uniqKey="Levy C" first="Carmit" last="Levy">Carmit Levy</name><affiliation><nlm:affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: carmitlevy@post.tau.ac.il.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of genetics and genomics = Yi chuan xue bao</title><idno type="ISSN">1673-8527</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">27297116</PMID><DateCreated><Year>2016</Year><Month>06</Month><Day>28</Day></DateCreated><DateRevised><Year>2016</Year><Month>06</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1673-8527</ISSN><JournalIssue CitedMedium="Internet"><Volume>43</Volume><Issue>6</Issue><PubDate><Year>2016</Year><Month>Jun</Month><Day>20</Day></PubDate></JournalIssue><Title>Journal of genetics and genomics = Yi chuan xue bao</Title><ISOAbbreviation>J Genet Genomics</ISOAbbreviation></Journal><ArticleTitle>Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.</ArticleTitle><Pagination><MedlinePgn>369-79</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jgg.2016.05.005</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1673-8527(16)30056-X</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright © 2016. Published by Elsevier Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Levin</LastName><ForeName>Lotan</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Srour</LastName><ForeName>Shani</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gartner</LastName><ForeName>Jared</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kapitansky</LastName><ForeName>Oxana</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qutob</LastName><ForeName>Nouar</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dror</LastName><ForeName>Shani</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Golan</LastName><ForeName>Tamar</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dayan</LastName><ForeName>Roy</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brener</LastName><ForeName>Ronen</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Oncology Institute, Edith Wolfson Medical Center, Holon 5822012, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ziv</LastName><ForeName>Tamar</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Technion Smoler Proteomics Center, Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khaled</LastName><ForeName>Mehdi</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut Gustave Roussy, INSERM U753, Villejuif 94805, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schueler-Furman</LastName><ForeName>Ora</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Samuels</LastName><ForeName>Yardena</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Levy</LastName><ForeName>Carmit</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: carmitlevy@post.tau.ac.il.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>05</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>China</Country><MedlineTA>J Genet Genomics</MedlineTA><NlmUniqueID>101304616</NlmUniqueID><ISSNLinking>1673-8527</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Melanoma</Keyword><Keyword MajorTopicYN="N">Mutation</Keyword><Keyword MajorTopicYN="N">Parkin</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>10</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>05</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>05</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>6</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>6</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>6</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27297116</ArticleId><ArticleId IdType="pii">S1673-8527(16)30056-X</ArticleId><ArticleId IdType="doi">10.1016/j.jgg.2016.05.005</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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