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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Bibliographic Details
Published in:Scientific reports 2017-03, Vol.7, p.44539
Main Authors: Ahmed, Abrar, Wan, Xiaochun, Mitxitorena, Izaskun, Lindsay, Andrew J, Paolo Pandolfi, Pier, Mccaffrey, Mary W, Keeshan, Karen, Chen, Youhai H, Carmody, Ruaidhrí J
Format: Article
Language:English
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
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Summary: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.
ISSN:2045-2322
DOI:10.1038/srep44539