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Sci Rep. 2017 Mar 20;7:44539. doi: 10.1038/srep44539.

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

Author information

1
Department of Biochemistry, University College Cork, Cork, Ireland.
2
Shenzhen Institutes of Advanced Technology, Shenzhen, China.
3
GLAZgo Discovery Centre, Institute of Infection, Immunity &Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
4
Department of Pathology, Beth Israel Deaconess Medical Centre, Harvard University, Boston, MA, 02215, USA.
5
Paul O'Gorman Leukaemia Research Centre, College of Medicine, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, United Kingdom.
6
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
7
Centre for Immunobiology, Institute of Infection, Immunity &Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

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.

PMID:
28317833
PMCID:
PMC5357907
DOI:
10.1038/srep44539
[Indexed for MEDLINE]
Free PMC Article

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