A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins
PML and Tif1a are fused to RARA and Braf , respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dep...
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| Veröffentlicht in: | Nature genetics 1999-11, Vol.23 (3), p.287-295 |
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| container_title | Nature genetics |
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| creator | Kalantry, Sundeep Gandini, Domenica Freedman, Leonard P Cenciarelli, Cristina Delva, Laurent Rachez, Christophe Zhang, Hui Zhong, Sue Pandolfi, Pier Paolo |
| description | PML
and
Tif1a
are fused to
RARA
and
Braf
, respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRα/RARα. PML interacts with Tif1α and CBP. In
Pml
–/–
cells, the RA-dependent induction of genes such as
RARB2
and the ability of Tif1α and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1α are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARα, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL). |
| doi_str_mv | 10.1038/15463 |
| format | Article |
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and
Tif1a
are fused to
RARA
and
Braf
, respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRα/RARα. PML interacts with Tif1α and CBP. In
Pml
–/–
cells, the RA-dependent induction of genes such as
RARB2
and the ability of Tif1α and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1α are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARα, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL).</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/15463</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Braf gene ; Cancer Research ; CBP protein ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Human Genetics ; Molecular and cellular biology ; PML gene ; RARA gene ; RARB2 gene ; Tif1^a gene</subject><ispartof>Nature genetics, 1999-11, Vol.23 (3), p.287-295</ispartof><rights>Nature America Inc. 1999</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-518284135d14684450ae3988aad064370be472af4f108c641bcb1785b8c7282c3</citedby><cites>FETCH-LOGICAL-c335t-518284135d14684450ae3988aad064370be472af4f108c641bcb1785b8c7282c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/15463$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/15463$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1188170$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Kalantry, Sundeep</creatorcontrib><creatorcontrib>Gandini, Domenica</creatorcontrib><creatorcontrib>Freedman, Leonard P</creatorcontrib><creatorcontrib>Cenciarelli, Cristina</creatorcontrib><creatorcontrib>Delva, Laurent</creatorcontrib><creatorcontrib>Rachez, Christophe</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Zhong, Sue</creatorcontrib><creatorcontrib>Pandolfi, Pier Paolo</creatorcontrib><title>A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><description>PML
and
Tif1a
are fused to
RARA
and
Braf
, respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRα/RARα. PML interacts with Tif1α and CBP. In
Pml
–/–
cells, the RA-dependent induction of genes such as
RARB2
and the ability of Tif1α and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1α are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARα, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL).</description><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Braf gene</subject><subject>Cancer Research</subject><subject>CBP protein</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Human Genetics</subject><subject>Molecular and cellular biology</subject><subject>PML gene</subject><subject>RARA gene</subject><subject>RARB2 gene</subject><subject>Tif1^a gene</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNplkMtOwzAQRSMEEuXxD14AKwKe2EncZYV4SUWgCtaR60xKqtQOHofHZ_EjfBOGIliwmhndo3s1N0n2gZ8AF-oUclmIjWT0NVMoQW3GnReQSi6K7WSHaMk5SMnVKKEJm03SGnu0NdpwzMKwcoNPF969hEdGQ997JGqfkQWvLRnf9qF1lhm36jt8ZS2x8BhF7RcYmGu-r7ubaTqbzD7embY1uwfFnDWu9y5ga2kv2Wp0R7j_M3eTh4vz-7OrdHp7eX02maZGiDykOahMSRB5DbJQUuZcoxgrpXXNCylKPkdZZrqRDXBlCglzM4dS5XNlykxlRuwmR2vfGPw0IIVq1ZLBrtMW3UAVlJIXWQYRPFyDxjsij03V-3al_VsFvPqqtPquNHIHP4aajO6aWIhp6Q8GpaDkf7kUFbtAXy1jpTa--s-PrUGrw-Dx18guAMbjKlOl-AR6RowB</recordid><startdate>19991101</startdate><enddate>19991101</enddate><creator>Kalantry, Sundeep</creator><creator>Gandini, Domenica</creator><creator>Freedman, Leonard P</creator><creator>Cenciarelli, Cristina</creator><creator>Delva, Laurent</creator><creator>Rachez, Christophe</creator><creator>Zhang, Hui</creator><creator>Zhong, Sue</creator><creator>Pandolfi, Pier Paolo</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19991101</creationdate><title>A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins</title><author>Kalantry, Sundeep ; Gandini, Domenica ; Freedman, Leonard P ; Cenciarelli, Cristina ; Delva, Laurent ; Rachez, Christophe ; Zhang, Hui ; Zhong, Sue ; Pandolfi, Pier Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-518284135d14684450ae3988aad064370be472af4f108c641bcb1785b8c7282c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Braf gene</topic><topic>Cancer Research</topic><topic>CBP protein</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Human Genetics</topic><topic>Molecular and cellular biology</topic><topic>PML gene</topic><topic>RARA gene</topic><topic>RARB2 gene</topic><topic>Tif1^a gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kalantry, Sundeep</creatorcontrib><creatorcontrib>Gandini, Domenica</creatorcontrib><creatorcontrib>Freedman, Leonard P</creatorcontrib><creatorcontrib>Cenciarelli, Cristina</creatorcontrib><creatorcontrib>Delva, Laurent</creatorcontrib><creatorcontrib>Rachez, Christophe</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Zhong, Sue</creatorcontrib><creatorcontrib>Pandolfi, Pier Paolo</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kalantry, Sundeep</au><au>Gandini, Domenica</au><au>Freedman, Leonard P</au><au>Cenciarelli, Cristina</au><au>Delva, Laurent</au><au>Rachez, Christophe</au><au>Zhang, Hui</au><au>Zhong, Sue</au><au>Pandolfi, Pier Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><date>1999-11-01</date><risdate>1999</risdate><volume>23</volume><issue>3</issue><spage>287</spage><epage>295</epage><pages>287-295</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>PML
and
Tif1a
are fused to
RARA
and
Braf
, respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRα/RARα. PML interacts with Tif1α and CBP. In
Pml
–/–
cells, the RA-dependent induction of genes such as
RARB2
and the ability of Tif1α and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1α are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARα, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL).</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><doi>10.1038/15463</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 1999-11, Vol.23 (3), p.287-295 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17406221 |
| source | Nature; SpringerLink Journals - AutoHoldings |
| subjects | Agriculture Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Braf gene Cancer Research CBP protein Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Fundamental and applied biological sciences. Psychology Gene Function Human Genetics Molecular and cellular biology PML gene RARA gene RARB2 gene Tif1^a gene |
| title | A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins |
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