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Regulation of NF-[kappa]B by PML and PML-RAR[alpha]
Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional response...
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Published in: | Scientific reports 2017-03, Vol.7, p.44539 |
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creator | Ahmed, Abrar Wan, Xiaochun Mitxitorena, Izaskun Lindsay, Andrew J Paolo Pandolfi, Pier Mccaffrey, Mary W Keeshan, Karen Chen, Youhai H Carmody, Ruaidhrí J |
description | Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML-/- cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB. |
doi_str_mv | 10.1038/srep44539 |
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This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB.</description><subject>Acute promyeloid leukemia</subject><subject>Cell differentiation</subject><subject>Chromatin</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene expression</subject><subject>Leukemia</subject><subject>NF-κB protein</subject><subject>Nuclear transport</subject><subject>Phosphorylation</subject><subject>Promyeloid leukemia</subject><subject>Retinoic acid receptors</subject><subject>Transcription</subject><subject>Translocation</subject><subject>Tumors</subject><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpjYBA0NNAzNDC20C8uSi0wMTE1tmRi4DQyMDHVNTI2MuJg4C0uzjIAAlMjSxNDS04G46DU9NKcxJLM_DyF_DQFPzfd6OzEgoLEWCeFpEqFAF8fhcS8FBCtG-QYFJ2YU5CRGMvDwJqWmFOcyguluRmU3VxDnD10C4ryC0tTi0vis_JLi_KAUvGGlgbGxuYWhiaGxsSpAgBRfTaC</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Ahmed, Abrar</creator><creator>Wan, Xiaochun</creator><creator>Mitxitorena, Izaskun</creator><creator>Lindsay, Andrew J</creator><creator>Paolo Pandolfi, Pier</creator><creator>Mccaffrey, Mary W</creator><creator>Keeshan, Karen</creator><creator>Chen, Youhai H</creator><creator>Carmody, Ruaidhrí J</creator><general>Nature Publishing Group</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20170301</creationdate><title>Regulation of NF-[kappa]B by PML and PML-RAR[alpha]</title><author>Ahmed, Abrar ; 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PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML-/- cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><doi>10.1038/srep44539</doi><oa>free_for_read</oa></addata></record> |
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subjects | Acute promyeloid leukemia Cell differentiation Chromatin Deoxyribonucleic acid DNA Gene expression Leukemia NF-κB protein Nuclear transport Phosphorylation Promyeloid leukemia Retinoic acid receptors Transcription Translocation Tumors |
title | Regulation of NF-[kappa]B by PML and PML-RAR[alpha] |
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