Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells*
Identifieur interne : 000817 ( Pmc/Checkpoint ); précédent : 000816; suivant : 000818Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells*
Auteurs : Yasaman Aghazadeh ; Malena B. Rone ; Josip Blonder ; Xiaoying Ye ; Timothy D. Veenstra ; D. Buck Hales ; Martine Culty ; Vassilios PapadopoulosSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2012.
Abstract
Url:
DOI: 10.1074/jbc.M112.339580
PubMed: 22427666
PubMed Central: 3346089
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Aghazadeh, Yasaman" sort="Aghazadeh, Yasaman" uniqKey="Aghazadeh Y" first="Yasaman" last="Aghazadeh">Yasaman Aghazadeh</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rone, Malena B" sort="Rone, Malena B" uniqKey="Rone M" first="Malena B." last="Rone">Malena B. Rone</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Blonder, Josip" sort="Blonder, Josip" uniqKey="Blonder J" first="Josip" last="Blonder">Josip Blonder</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Ye, Xiaoying" sort="Ye, Xiaoying" uniqKey="Ye X" first="Xiaoying" last="Ye">Xiaoying Ye</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Veenstra, Timothy D" sort="Veenstra, Timothy D" uniqKey="Veenstra T" first="Timothy D." last="Veenstra">Timothy D. Veenstra</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Hales, D Buck" sort="Hales, D Buck" uniqKey="Hales D" first="D. Buck" last="Hales">D. Buck Hales</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Culty, Martine" sort="Culty, Martine" uniqKey="Culty M" first="Martine" last="Culty">Martine Culty</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Papadopoulos, Vassilios" sort="Papadopoulos, Vassilios" uniqKey="Papadopoulos V" first="Vassilios" last="Papadopoulos">Vassilios Papadopoulos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22427666</idno><idno type="pmc">3346089</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346089</idno><idno type="RBID">PMC:3346089</idno><idno type="doi">10.1074/jbc.M112.339580</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000564</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000564</idno><idno type="wicri:Area/Pmc/Curation">000564</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000564</idno><idno type="wicri:Area/Pmc/Checkpoint">000817</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000817</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Aghazadeh, Yasaman" sort="Aghazadeh, Yasaman" uniqKey="Aghazadeh Y" first="Yasaman" last="Aghazadeh">Yasaman Aghazadeh</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rone, Malena B" sort="Rone, Malena B" uniqKey="Rone M" first="Malena B." last="Rone">Malena B. Rone</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Blonder, Josip" sort="Blonder, Josip" uniqKey="Blonder J" first="Josip" last="Blonder">Josip Blonder</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Ye, Xiaoying" sort="Ye, Xiaoying" uniqKey="Ye X" first="Xiaoying" last="Ye">Xiaoying Ye</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Veenstra, Timothy D" sort="Veenstra, Timothy D" uniqKey="Veenstra T" first="Timothy D." last="Veenstra">Timothy D. Veenstra</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Hales, D Buck" sort="Hales, D Buck" uniqKey="Hales D" first="D. Buck" last="Hales">D. Buck Hales</name><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Culty, Martine" sort="Culty, Martine" uniqKey="Culty M" first="Martine" last="Culty">Martine Culty</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Papadopoulos, Vassilios" sort="Papadopoulos, Vassilios" uniqKey="Papadopoulos V" first="Vassilios" last="Papadopoulos">Vassilios Papadopoulos</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> The mechanism mediating hormone-induced steroidogenesis involves multiprotein complexes.</p><p><bold>Results:</bold> 14-3-3γ is identified as a hormone-induced regulator of STAR function.</p><p><bold>Conclusion:</bold> 14-3-3γ negatively regulates steroidogenesis by interacting with STAR, acting in a buffer capacity to sustain the STAR-mediated steroid formation for prolonged periods of time.</p><p><bold>Significance:</bold> Characterizing the mechanisms regulating steroidogenesis contributes to our understanding of how steroids are synthesized.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22427666</article-id><article-id pub-id-type="pmc">3346089</article-id><article-id pub-id-type="publisher-id">M112.339580</article-id><article-id pub-id-type="doi">10.1074/jbc.M112.339580</article-id><article-categories><subj-group subj-group-type="heading"><subject>Metabolism</subject></subj-group></article-categories><title-group><article-title>Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">14-3-3γ-STAR interaction in Steroidogenesis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Aghazadeh</surname><given-names>Yasaman</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rone</surname><given-names>Malena B.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN3"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Blonder</surname><given-names>Josip</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ye</surname><given-names>Xiaoying</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Veenstra</surname><given-names>Timothy D.</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hales</surname><given-names>D. Buck</given-names></name><xref ref-type="aff" rid="aff5"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Culty</surname><given-names>Martine</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Papadopoulos</surname><given-names>Vassilios</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>‖</sup></xref><xref ref-type="aff" rid="aff3">**</xref><xref ref-type="corresp" rid="cor1"><sup>3</sup></xref></contrib><aff id="aff1">From<label>‡</label>The Research Institute of the McGill University Health Centre and the Department of Medicine,</aff><aff id="aff2">the<label>‖</label>Department of Pharmacology and Therapeutics, and</aff><aff id="aff3">the<label>**</label>Department of Biochemistry, McGill University, Montreal, Quebec H3G 1A4, Canada,</aff><aff id="aff4">the<label>§</label>Laboratory of Proteomics and Analytical Technologies, Advanced Technologies Program, SAIC-Frederick Inc., NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, and</aff><aff id="aff5">the<label>¶</label>Department of Physiology, Southern Illinois University, School of Medicine, Carbondale, Illinois 62901</aff></contrib-group><author-notes><corresp id="cor1"><label>3</label> To whom correspondence should be addressed: <addr-line>The Research Institute of the McGill University Health Center, 1650 Cedar Ave., C10-148, Montreal, Quebec H3G 1A4, Canada.</addr-line> Tel.: <phone>514-934-1934 (ext. 44580)</phone>; Fax: <fax>514-934-8439</fax>; E-mail: <email>vassilios.papadopoulos@mcgill.ca</email>.</corresp><fn fn-type="supported-by" id="FN2"><label>1</label><p>Supported in part by a predoctoral fellowship from the Research Institute of McGill University Health Centre.</p></fn><fn fn-type="supported-by" id="FN3"><label>2</label><p>Supported in part by a postdoctoral fellowship from the Research Institute of McGill University Health Centre.</p></fn></author-notes><pub-date pub-type="ppub"><day>4</day><month>5</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>16</day><month>3</month><year>2012</year></pub-date><volume>287</volume><issue>19</issue><fpage>15380</fpage><lpage>15394</lpage><history><date date-type="received"><day>3</day><month>1</month><year>2012</year></date><date date-type="rev-recd"><day>27</day><month>2</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01912015380.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> The mechanism mediating hormone-induced steroidogenesis involves multiprotein complexes.</p><p><bold>Results:</bold> 14-3-3γ is identified as a hormone-induced regulator of STAR function.</p><p><bold>Conclusion:</bold> 14-3-3γ negatively regulates steroidogenesis by interacting with STAR, acting in a buffer capacity to sustain the STAR-mediated steroid formation for prolonged periods of time.</p><p><bold>Significance:</bold> Characterizing the mechanisms regulating steroidogenesis contributes to our understanding of how steroids are synthesized.</p></abstract><abstract><p>Cholesterol is the sole precursor of steroid hormones in the body. The import of cholesterol to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis, relies on the formation of a protein complex that assembles at the outer mitochondrial membrane called the transduceosome. The transduceosome contains several mitochondrial and cytosolic components, including the steroidogenic acute regulatory protein (STAR). Human chorionic gonadotropin (hCG) induces <italic>de novo</italic> synthesis of STAR, a process shown to parallel maximal steroid production. In the hCG-dependent steroidogenic MA-10 mouse Leydig cell line, the 14-3-3γ protein was identified in native mitochondrial complexes by mass spectrometry and immunoblotting, and its levels increased in response to hCG treatment. The 14-3-3 proteins bind and regulate the activity of many proteins, acting via target protein activation, modification and localization. In MA-10 cells, cAMP induces 14-3-3γ expression parallel to STAR expression. Silencing of 14-3-3γ expression potentiates hormone-induced steroidogenesis. Binding motifs of 14-3-3γ were identified in components of the transduceosome, including STAR. Immunoprecipitation studies demonstrate a hormone-dependent interaction between 14-3-3γ and STAR that coincides with reduced 14-3-3γ homodimerization. The binding site of 14-3-3γ on STAR was identified to be Ser-194 in the STAR-related sterol binding lipid transfer (START) domain, the site phosphorylated in response to hCG. Taken together, these results demonstrate that 14-3-3γ negatively regulates steroidogenesis by binding to Ser-194 of STAR, thus keeping STAR in an unfolded state, unable to induce maximal steroidogenesis. Over time 14-3-3γ homodimerizes and dissociates from STAR, allowing this protein to induce maximal mitochondrial steroid formation.</p></abstract><kwd-group><kwd>Cholesterol</kwd><kwd>Hormones</kwd><kwd>Mitochondrial Transport</kwd><kwd>Steroidogenesis</kwd><kwd>Testis</kwd><kwd>14-3-3 Proteins</kwd><kwd>Steroidogenic Acute Regulatory Protein</kwd><kwd>Translocator Protein</kwd></kwd-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Aghazadeh, Yasaman" sort="Aghazadeh, Yasaman" uniqKey="Aghazadeh Y" first="Yasaman" last="Aghazadeh">Yasaman Aghazadeh</name><name sortKey="Blonder, Josip" sort="Blonder, Josip" uniqKey="Blonder J" first="Josip" last="Blonder">Josip Blonder</name><name sortKey="Culty, Martine" sort="Culty, Martine" uniqKey="Culty M" first="Martine" last="Culty">Martine Culty</name><name sortKey="Hales, D Buck" sort="Hales, D Buck" uniqKey="Hales D" first="D. Buck" last="Hales">D. Buck Hales</name><name sortKey="Papadopoulos, Vassilios" sort="Papadopoulos, Vassilios" uniqKey="Papadopoulos V" first="Vassilios" last="Papadopoulos">Vassilios Papadopoulos</name><name sortKey="Rone, Malena B" sort="Rone, Malena B" uniqKey="Rone M" first="Malena B." last="Rone">Malena B. Rone</name><name sortKey="Veenstra, Timothy D" sort="Veenstra, Timothy D" uniqKey="Veenstra T" first="Timothy D." last="Veenstra">Timothy D. Veenstra</name><name sortKey="Ye, Xiaoying" sort="Ye, Xiaoying" uniqKey="Ye X" first="Xiaoying" last="Ye">Xiaoying Ye</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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