Promyelocytic Leukemia Protein Isoform II Promotes Transcription Factor Recruitment To Activate Interferon Beta and Interferon-Responsive Gene Expression

Molecular and Cellular Biology
Yixiang ChenKeith N Leppard

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 leukemia (PML) protein has been implicated in these responses, although its role has not been defined. Here, we show that PML isoform II (PML-II) is specifically required for efficient induction of IFN-β 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 coactivator CREB-binding protein (CBP), to facilitate transcriptional complex formation. The absence of PML-II substantially reduced binding of these factors and IFN regulatory factor 3 (IRF3) to IFN-β or ISGs promoters and sharply reduced gene activation. The unique C-terminal domain 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...Continue Reading

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Citations

Apr 8, 2016·Journal of Virology·Myriam Scherer, Thomas Stamminger
Mar 11, 2020·Frontiers in Cellular and Infection Microbiology·Lucile G Guion, Martin Sapp
Apr 4, 2021·Veterinary Sciences·Sabari Nath Neerukonda
Aug 8, 2021·Cells·Kuo-Chieh Liao, Mariano A Garcia-Blanco
Jul 4, 2021·Cell Communication and Signaling : CCS·Xueqiong MengKeith Leppard

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Methods Mentioned

BETA
Assay
transfection
confocal microscopy
immunoprecipitation
PCR
nuclear translocation
ChIP

Software Mentioned

QuantityOne
Leica

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