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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2</title><author><name sortKey="Clements, Casey M" sort="Clements, Casey M" uniqKey="Clements C" first="Casey M." last="Clements">Casey M. Clements</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Mcnally, Richard S" sort="Mcnally, Richard S" uniqKey="Mcnally R" first="Richard S." last="Mcnally">Richard S. Mcnally</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Conti, Brian J" sort="Conti, Brian J" uniqKey="Conti B" first="Brian J." last="Conti">Brian J. Conti</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, University Health Network, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1</nlm:aff></affiliation></author><author><name sortKey="Ting, Jenny P Y" sort="Ting, Jenny P Y" uniqKey="Ting J" first="Jenny P.-Y." last="Ting">Jenny P.-Y. Ting</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17015834</idno><idno type="pmc">1586179</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1586179</idno><idno type="RBID">PMC:1586179</idno><idno type="doi">10.1073/pnas.0607260103</idno><date when="2006">2006</date><idno type="wicri:Area/Pmc/Corpus">000678</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000678</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2</title><author><name sortKey="Clements, Casey M" sort="Clements, Casey M" uniqKey="Clements C" first="Casey M." last="Clements">Casey M. Clements</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Mcnally, Richard S" sort="Mcnally, Richard S" uniqKey="Mcnally R" first="Richard S." last="Mcnally">Richard S. Mcnally</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Conti, Brian J" sort="Conti, Brian J" uniqKey="Conti B" first="Brian J." last="Conti">Brian J. Conti</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation><nlm:aff id="aff2">The Campbell Family Institute for Breast Cancer Research, University Health Network, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1</nlm:aff></affiliation></author><author><name sortKey="Ting, Jenny P Y" sort="Ting, Jenny P Y" uniqKey="Ting J" first="Jenny P.-Y." last="Ting">Jenny P.-Y. Ting</name><affiliation><nlm:aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>DJ-1/PARK7, a cancer- and Parkinson's disease (PD)-associated protein, protects cells from toxic stresses. However, the functional basis of this protection has remained elusive. We found that loss of DJ-1 leads to deficits in NQO1 [NAD(P)H quinone oxidoreductase 1], a detoxification enzyme. This deficit is attributed to a loss of Nrf2 (nuclear factor erythroid 2-related factor), a master regulator of antioxidant transcriptional responses. DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination. Without intact DJ-1, Nrf2 protein is unstable, and transcriptional responses are thereby decreased both basally and after induction. This effect of DJ-1 on Nrf2 is present in both transformed lines and primary cells across human and mouse species. DJ-1's effect on Nrf2 and subsequent effects on antioxidant responses may explain how DJ-1 affects the etiology of both cancer and PD, which are seemingly disparate disorders. Furthermore, this DJ-1/Nrf2 functional axis presents a therapeutic target in cancer treatment and justifies DJ-1 as a tumor biomarker.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17015834</article-id><article-id pub-id-type="pmc">1586179</article-id><article-id pub-id-type="publisher-id">3698</article-id><article-id pub-id-type="doi">10.1073/pnas.0607260103</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Cell Biology</subject></subj-group></subj-group></article-categories><title-group><article-title>DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Clements</surname><given-names>Casey M.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>McNally</surname><given-names>Richard S.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Conti</surname><given-names>Brian J.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>Tak W.</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="corresp" rid="cor1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ting</surname><given-names>Jenny P.-Y.</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="corresp" rid="cor1"><sup>‡</sup></xref></contrib><aff id="aff1">*Department of Microbiology–Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295; and</aff><aff id="aff2"><sup>†</sup>The Campbell Family Institute for Breast Cancer Research, University Health Network, 620 University Avenue, Suite 706, Toronto, ON, Canada M5G 2C1</aff></contrib-group><author-notes><corresp id="cor1"><sup>‡</sup>To whom correspondence may be addressed. E-mail:
<email>tmak@uhnresearch.ca</email> or <email>jenny_ting@med.unc.edu</email></corresp><fn fn-type="con"><p>Contributed by Tak W. Mak, August 22, 2006</p></fn><fn fn-type="con"><p>Author contributions: C.M.C., T.W.M., and J.P.-Y.T. designed research; C.M.C., R.S.M., and B.J.C. performed research; T.W.M. contributed new reagents/analytic tools; C.M.C., R.S.M., and B.J.C. analyzed data; and C.M.C. and J.P.-Y.T. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>10</day><month>10</month><year>2006</year></pub-date><pub-date pub-type="epub"><day>2</day><month>10</month><year>2006</year></pub-date><volume>103</volume><issue>41</issue><fpage>15091</fpage><lpage>15096</lpage><copyright-statement>© 2006 by The National Academy of Sciences of the USA</copyright-statement><copyright-year>2006</copyright-year><license license-type="open-access"><p>Freely available online through the PNAS open access option.</p></license><self-uri xlink:title="pdf" xlink:href="zpq04106015091.pdf"></self-uri><abstract><p>DJ-1/PARK7, a cancer- and Parkinson's disease (PD)-associated protein, protects cells from toxic stresses. However, the functional basis of this protection has remained elusive. We found that loss of DJ-1 leads to deficits in NQO1 [NAD(P)H quinone oxidoreductase 1], a detoxification enzyme. This deficit is attributed to a loss of Nrf2 (nuclear factor erythroid 2-related factor), a master regulator of antioxidant transcriptional responses. DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination. Without intact DJ-1, Nrf2 protein is unstable, and transcriptional responses are thereby decreased both basally and after induction. This effect of DJ-1 on Nrf2 is present in both transformed lines and primary cells across human and mouse species. DJ-1's effect on Nrf2 and subsequent effects on antioxidant responses may explain how DJ-1 affects the etiology of both cancer and PD, which are seemingly disparate disorders. Furthermore, this DJ-1/Nrf2 functional axis presents a therapeutic target in cancer treatment and justifies DJ-1 as a tumor biomarker.</p></abstract><kwd-group><kwd>oxidative stress</kwd><kwd>PARK7</kwd><kwd>NQO1</kwd><kwd>Keap1</kwd><kwd>neurodegeneration</kwd></kwd-group><custom-meta-wrap><custom-meta><meta-name>PDF</meta-name><meta-value><uri xlink:type="simple" xlink:href="zpq04106015091.pdf"></uri></meta-value></custom-meta></custom-meta-wrap></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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