Role of PML in Cell Growth and the Retinoic Acid Pathway
The PML gene is fused to the retinoic acid receptor α (RARα) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorige...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1998-03, Vol.279 (5356), p.1547-1551 |
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| creator | Wang, Zhu Gang Delva, Laurent Gaboli, Mirella Rivi, Roberta Giorgio, Marco Cordon-Cardo, Carlos Grosveld, Frank Pandolfi, Pier Paolo |
| description | The PML gene is fused to the retinoic acid receptor α (RARα) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21$^{WAF1/CIP1}$ gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARα fusion protein may be important in APL pathogenesis. |
| doi_str_mv | 10.1126/science.279.5356.1547 |
| format | Article |
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Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21$^{WAF1/CIP1}$ gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARα fusion protein may be important in APL pathogenesis.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.279.5356.1547</identifier><identifier>PMID: 9488655</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Acids ; Acute leukemia, Promyelocytic ; Acute myelocytic leukemia ; Animals ; Apoptosis ; B lymphocytes ; Biological and medical sciences ; Carcinogenesis ; Cell Differentiation - drug effects ; Cell Division ; Cell growth ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cellular biology ; Cultured cells ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins - genetics ; Female ; Fibroblasts - cytology ; Fundamental and applied biological sciences. Psychology ; Gene Targeting ; Genes ; Genetic aspects ; Granulocytes - cytology ; Hematopoiesis ; Hematopoietic Stem Cells - cytology ; Individualized Instruction ; Leukemia, Promyelocytic, Acute - pathology ; Logical Thinking ; Lymphoma ; Male ; Mice ; Molecular and cellular biology ; Monocytes - cytology ; Myeloid cells ; Neoplasm Proteins - genetics ; Neoplasm Proteins - physiology ; Neoplasms, Experimental - etiology ; Nuclear Proteins ; Oncogene Proteins, Fusion - physiology ; Papilloma ; Pathology ; Promyelocytic Leukemia Protein ; Stem cells ; T lymphocytes ; Transcription Factors - genetics ; Transcription Factors - physiology ; Transcriptional Activation ; Tretinoin - pharmacology ; Tretinoin - physiology ; Tumor Suppressor Proteins ; Tumors</subject><ispartof>Science (American Association for the Advancement of Science), 1998-03, Vol.279 (5356), p.1547-1551</ispartof><rights>Copyright 1998 American Association for the Advancement of Science</rights><rights>1998 INIST-CNRS</rights><rights>COPYRIGHT 1998 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1998 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Mar 6, 1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c837t-c28e8f13752c15d9febf378a98d6672c454dff600dcc09a166e66cd7265467f93</citedby><cites>FETCH-LOGICAL-c837t-c28e8f13752c15d9febf378a98d6672c454dff600dcc09a166e66cd7265467f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2893795$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2893795$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2175097$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9488655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Zhu Gang</creatorcontrib><creatorcontrib>Delva, Laurent</creatorcontrib><creatorcontrib>Gaboli, Mirella</creatorcontrib><creatorcontrib>Rivi, Roberta</creatorcontrib><creatorcontrib>Giorgio, Marco</creatorcontrib><creatorcontrib>Cordon-Cardo, Carlos</creatorcontrib><creatorcontrib>Grosveld, Frank</creatorcontrib><creatorcontrib>Pandolfi, Pier Paolo</creatorcontrib><title>Role of PML in Cell Growth and the Retinoic Acid Pathway</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The PML gene is fused to the retinoic acid receptor α (RARα) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21$^{WAF1/CIP1}$ gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARα fusion protein may be important in APL pathogenesis.</description><subject>Acids</subject><subject>Acute leukemia, Promyelocytic</subject><subject>Acute myelocytic leukemia</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>B lymphocytes</subject><subject>Biological and medical sciences</subject><subject>Carcinogenesis</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Division</subject><subject>Cell growth</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cultured cells</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - genetics</subject><subject>Female</subject><subject>Fibroblasts - cytology</subject><subject>Fundamental and applied biological sciences. 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genetics</subject><subject>Transcription Factors - physiology</subject><subject>Transcriptional Activation</subject><subject>Tretinoin - pharmacology</subject><subject>Tretinoin - physiology</subject><subject>Tumor Suppressor Proteins</subject><subject>Tumors</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0luLEzEUB_BBlLWufgMXBlnUh52ay-T2WIvWhWqX9fIaspmTNmU6WZMp6357U1pWKkVLHgI5v5wk5F8UZxgNMSb8XbIeOgtDItSQUcaHmNXiUTHASLFKEUQfFwOEKK8kEuxp8SylJUK5puhJcaJqKTljg0JehxbK4Mqrz9PSd-UY2racxHDXL0rTNWW_gPIaet8Fb8uR9U15ZfrFnbl_Xjxxpk3wYjefFt8_fvg2_lRNZ5PL8WhaWUlFX1kiQTpMBSMWs0Y5uHFUSKNkw7kgtmZ14xxHqLEWKYM5B85tIwhnNRdO0dPi9bbvbQw_15B6vfLJ5luaDsI6aaEErhnDGb75N6ypoPlM8d-WmFPClEQZvvoLLsM6dvm5mmDKhMCozuhii-amBe07F_po7Bw6iKYNHTifl0cE1YTUdMOrAzyPBlbeHvJv93wmPfzq52adkr78-uVoOvtxNH0_OZbKyXSPXhyiNrQtzEHnXIxne5xtuY0hpQhO30a_MvFeY6Q3Gde7jOuccb3JuN5kPO87233L-mYFzcOuXahz_XxXN8ma1kXTWZ8eGMGCIbVp83LLlqkP8U9ZKioUo78BpecGXA</recordid><startdate>19980306</startdate><enddate>19980306</enddate><creator>Wang, Zhu Gang</creator><creator>Delva, Laurent</creator><creator>Gaboli, Mirella</creator><creator>Rivi, Roberta</creator><creator>Giorgio, Marco</creator><creator>Cordon-Cardo, Carlos</creator><creator>Grosveld, Frank</creator><creator>Pandolfi, Pier Paolo</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>0-V</scope><scope>3V.</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9-</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0K</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>7TO</scope><scope>7X8</scope></search><sort><creationdate>19980306</creationdate><title>Role of PML in Cell Growth and the Retinoic Acid Pathway</title><author>Wang, Zhu Gang ; Delva, Laurent ; Gaboli, Mirella ; Rivi, Roberta ; Giorgio, Marco ; Cordon-Cardo, Carlos ; Grosveld, Frank ; Pandolfi, Pier Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c837t-c28e8f13752c15d9febf378a98d6672c454dff600dcc09a166e66cd7265467f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Acids</topic><topic>Acute leukemia, Promyelocytic</topic><topic>Acute myelocytic leukemia</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>B lymphocytes</topic><topic>Biological and medical sciences</topic><topic>Carcinogenesis</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Division</topic><topic>Cell growth</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cell Transformation, Neoplastic</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Cultured cells</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - genetics</topic><topic>Female</topic><topic>Fibroblasts - cytology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Targeting</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Granulocytes - cytology</topic><topic>Hematopoiesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Individualized Instruction</topic><topic>Leukemia, Promyelocytic, Acute - pathology</topic><topic>Logical Thinking</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Monocytes - cytology</topic><topic>Myeloid cells</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - physiology</topic><topic>Neoplasms, Experimental - etiology</topic><topic>Nuclear Proteins</topic><topic>Oncogene Proteins, Fusion - physiology</topic><topic>Papilloma</topic><topic>Pathology</topic><topic>Promyelocytic Leukemia Protein</topic><topic>Stem cells</topic><topic>T lymphocytes</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><topic>Transcriptional 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Science)</jtitle><addtitle>Science</addtitle><date>1998-03-06</date><risdate>1998</risdate><volume>279</volume><issue>5356</issue><spage>1547</spage><epage>1551</epage><pages>1547-1551</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>The PML gene is fused to the retinoic acid receptor α (RARα) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21$^{WAF1/CIP1}$ gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARα fusion protein may be important in APL pathogenesis.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>9488655</pmid><doi>10.1126/science.279.5356.1547</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1998-03, Vol.279 (5356), p.1547-1551 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79714551 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | Acids Acute leukemia, Promyelocytic Acute myelocytic leukemia Animals Apoptosis B lymphocytes Biological and medical sciences Carcinogenesis Cell Differentiation - drug effects Cell Division Cell growth Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic Cells, Cultured Cellular biology Cultured cells Cyclin-Dependent Kinase Inhibitor p21 Cyclins - genetics Female Fibroblasts - cytology Fundamental and applied biological sciences. Psychology Gene Targeting Genes Genetic aspects Granulocytes - cytology Hematopoiesis Hematopoietic Stem Cells - cytology Individualized Instruction Leukemia, Promyelocytic, Acute - pathology Logical Thinking Lymphoma Male Mice Molecular and cellular biology Monocytes - cytology Myeloid cells Neoplasm Proteins - genetics Neoplasm Proteins - physiology Neoplasms, Experimental - etiology Nuclear Proteins Oncogene Proteins, Fusion - physiology Papilloma Pathology Promyelocytic Leukemia Protein Stem cells T lymphocytes Transcription Factors - genetics Transcription Factors - physiology Transcriptional Activation Tretinoin - pharmacology Tretinoin - physiology Tumor Suppressor Proteins Tumors |
| title | Role of PML in Cell Growth and the Retinoic Acid Pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T02%3A27%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Role%20of%20PML%20in%20Cell%20Growth%20and%20the%20Retinoic%20Acid%20Pathway&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Wang,%20Zhu%20Gang&rft.date=1998-03-06&rft.volume=279&rft.issue=5356&rft.spage=1547&rft.epage=1551&rft.pages=1547-1551&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.279.5356.1547&rft_dat=%3Cgale_proqu%3EA20422434%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213577104&rft_id=info:pmid/9488655&rft_galeid=A20422434&rft_jstor_id=2893795&rfr_iscdi=true |