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Promyelocytic leukemia protein isoform II promotes transcription factor recruitment to activate interferon β and interferon-responsive gene expression

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Chen, Yixiang, Wright, Jordan L., Meng, Xueqiong and Leppard, Keith (2015) Promyelocytic leukemia protein isoform II promotes transcription factor recruitment to activate interferon β and interferon-responsive gene expression. Molecular and Cellular Biology, Volume 35 (Number 10). pp. 1660-1672. doi:10.1128/MCB.01478-14 ISSN 0270-7306.

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Official URL: http://dx.doi.org/10.1128/MCB.01478-14

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Abstract

To trigger type I interferon (IFN) responses, pattern recognition receptors activate signaling cascades that lead to transcription of IFN and IFN-stimulated genes (ISGs). The promyelocytic leukaemia (PML) protein has been implicated in these responses though its role has not been defined. Here, we show that PML isoform II (PML-II) is specifically required for efficient induction of IFNβ transcription and of numerous ISGs, acting at the point of transcriptional complex assembly on target gene promoters. PML-II associated with specific transcription factors NF-κB and STAT1, as well as the co-activator CREB-binding protein (CBP), to facilitate transcriptional complex formation. The absence of PML-II substantially reduced binding of these factors and IRF3 to IFNβ or ISGs promoters and sharply reduced gene activation. The unique C-terminal exon of PML-II was essential for its activity while the N-terminal RBCC motif common to all PML isoforms was dispensable. We propose a model in which PML-II contributes to the transcription of multiple genes via the association of its C-terminal domain with relevant transcription complexes, which promotes the stable assembly of these complexes at promoters/enhancers of target genes and that in this way PML-II plays a significant role in the development of type I IFN responses.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Leukemia -- Genetic aspects, Leukemia -- Immunological aspects
Journal or Publication Title: Molecular and Cellular Biology
Publisher: American Society for Microbiology
ISSN: 0270-7306
Official Date: May 2015
Dates:
DateEvent
May 2015Published
2 March 2015Available
23 February 2015Accepted
10 December 2014Submitted
Volume: Volume 35
Number: Number 10
Number of Pages: 13
Page Range: pp. 1660-1672
DOI: 10.1128/MCB.01478-14
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 27 April 2016
Date of first compliant Open Access: 27 April 2016
Funder: Wellcome Trust (London, England), University of Warwick Postgraduate Research Scholarship, Great Britain-China Educational Trust, Sir Richard Stapley Educational Trust
Grant number: WT094713MA (WT)

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