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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
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Official URL: http://dx.doi.org/10.1128/MCB.01478-14
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 | ||||||||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology |
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| Divisions: | Faculty of 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: |
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| Date of first compliant deposit: | 27 April 2016 | ||||||||||
| 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 | ||||||||||
| 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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