Regulation of NF-κ B by PML and PML-RARα

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-κ B activity. TNFα-treated PML -/- cells show normal IκBα degradation and NF-κ B nuclear translocation but significantly reduced NF-κ B DNA binding and phosphorylation of NF-κ B 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-κ B. This study establishes PML as an important regulator of NF-κ B and demonstrates that PML-RARα dysregulates NF-κ B.