Ahmed, A;Wan, XC;Mitxitorena, I;Lindsay, AJ;Pandolfi, PP;McCaffrey, MW;Keeshan, K;Chen, YHH;Carmody, RJ

2017

March

Scientific Reports

Regulation of NF-kappa B by PML and PML-RAR alpha

Published

Altmetric: 14 ()

ACUTE PROMYELOCYTIC LEUKEMIA NUCLEAR-BODIES INTERPHASE NUCLEI IKK-EPSILON DNA-DAMAGE TRANSCRIPTION PHOSPHORYLATION ASSOCIATE APOPTOSIS DYNAMICS

7

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 TNF alpha-induced transcriptional responses by promoting NF-kappa B activity. TNF alpha-treated PML-/- cells show normal I kappa B alpha degradation and NF-kappa B nuclear translocation but significantly reduced NF-kappa B DNA binding and phosphorylation of NF-kappa B p65. We also demonstrate that the PML retinoic acid receptor-alpha (PML-RAR alpha) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNF alpha induced gene expression and phosphorylation of NF-kappa B. This study establishes PML as an important regulator of NF-kappa B and demonstrates that PML-RAR alpha dysregulates NF-kappa B.

LONDON

2045-2322

10.1038/srep44539