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)

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 > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Research
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
67108	1	Investigating NF-kB p50 phosphorylation and the regulation of transcription	Ruaidhri Carmody	Medical Research Council (MRC)	MR/M010694/1	III -IMMUNOLOGY
65983	1	Dissecting the function of Bcl-3 in NF-kappaB signaling in B cells	Ruaidhri Carmody	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/M003671/1	RI INFECTION IMMUNITY & INFLAMMATION