Regulation of NF-κB by PML and PML-RARα

Ahmed, A., Wan, X., Mitxitorena, I., Lindsay, A. J., Pandolfi, P. P., McCaffrey, M. W., Keeshan, K. , Chen, Y. H. and Carmody, R. J. (2017) Regulation of NF-κB by PML and PML-RARα. Scientific Reports, 7, 44539. (doi: 10.1038/srep44539) (PMID:28317833) (PMCID:PMC5357907)

[img]
Preview
Text
136735.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Carmody, Dr Ruaidhri and Keeshan, Dr Karen
Authors: Ahmed, A., Wan, X., Mitxitorena, I., Lindsay, A. J., Pandolfi, P. P., McCaffrey, M. W., Keeshan, K., Chen, Y. H., and Carmody, R. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7:44539
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
671081Investigating NF-kB p50 phosphorylation and the regulation of transcriptionRuaidhri CarmodyMedical Research Council (MRC)MR/M010694/1III -IMMUNOLOGY
659831Dissecting the function of Bcl-3 in NF-kappaB signaling in B cellsRuaidhri CarmodyBiotechnology and Biological Sciences Research Council (BBSRC)BB/M003671/1RI INFECTION IMMUNITY & INFLAMMATION