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Regulation of NF-κB by PML and PML-RARα.

ABSTRACT: 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.

SUBMITTER: Ahmed A

PROVIDER: S-EPMC5357907 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Regulation of NF-κB by PML and PML-RARα.

Ahmed Abrar A Wan Xiaochun X Mitxitorena Izaskun I Lindsay Andrew J AJ Paolo Pandolfi Pier P McCaffrey Mary W MW Keeshan Karen K Chen Youhai H YH Carmody Ruaidhrí J RJ

Scientific reports 20170320

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<sup>-/-</sup> cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κ ...[more]

PMID: 28317833

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PML regulates NF-κB transcriptional activity

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