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

Autor: Ahmed A; Department of Biochemistry, University College Cork, Cork, Ireland., Wan X; Shenzhen Institutes of Advanced Technology, Shenzhen, China., Mitxitorena I; GLAZgo Discovery Centre, Institute of Infection, Immunity &Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Lindsay AJ; Department of Biochemistry, University College Cork, Cork, Ireland., Paolo Pandolfi P; Department of Pathology, Beth Israel Deaconess Medical Centre, Harvard University, Boston, MA, 02215, USA., McCaffrey MW; Department of Biochemistry, University College Cork, Cork, Ireland., Keeshan K; Paul O'Gorman Leukaemia Research Centre, College of Medicine, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, United Kingdom., Chen YH; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Carmody RJ; Centre for Immunobiology, Institute of Infection, Immunity &Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Mar 20; Vol. 7, pp. 44539. Date of Electronic Publication: 2017 Mar 20.
DOI: 10.1038/srep44539
Abstrakt: 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.
Databáze: MEDLINE
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