DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation
Authors: Tai An
Shu Li
Po Tien
Wei Pan
Shuwen Wu
Bo Zhong
Hong-Bing Shu
Journal: PLoS Pathogens (2015)
Discipline: MICROBIOLOGY
Keywords: Viral infection; transcription factors; NF-Œ∫B; IRF3; type I interferons
Affiliations: The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan, China; The College of Basic Medical Science, Shaanxi University of Chinese Medicine, Xi'an, China., The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan, China.

Abstract:  Viral infection activates the transcription factors NF-Œ∫B and IRF3, which contribute to the induction of type I interferons (IFNs) and cellular antiviral responses. Protein kinases play a critical role in various signaling pathways by phosphorylating their substrates. Here, we identified dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2) as a negative regulator of virus-triggered type I IFN induction. DYRK2 inhibited the virus-triggered induction of type I IFNs and promoted the K48-linked ubiquitination and degradation of TANK-binding kinase 1 (TBK1) in a kinase-activity-dependent manner. We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1. These findings suggest that DYRK2 negatively regulates virus-triggered signaling by targeting TBK1 for phosphorylation and priming it for degradation, and these data provide new insights into the molecular mechanisms that dictate the cellular antiviral response. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. , 
 An additional concern: Figure 3 shows two panels that not only both match the 100 photos in the Stock Photo library, but that also appear to overlap with each other. * Two panels are showing the  TW06 - The Catch and the Map photo. Overlap is shown with red boxes. * Two panels are showing the  TW14 - Necklace photo, although there is no overlap.  , 
 This article has been withdrawn at the beginning of August 2020. The retraction notice is not linked to the article, but can be found here: https: www.europeanreview.org article 22450 It reads:  *Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cLong non-coding RNA MNX1-AS1 promotes migration and invasion of esophageal squamous cell carcinoma by upregulating IGF2, by D.-N. Zheng, C.-J. Zhang, G.-P. Sun, published in Eur Rev Med Pharmacol Sci 2019; 23 (14): 6179-6185u2013DOI: 10.26355 eurrev_201907_18431u2013PMID: 31364117u201d has been withdrawn.* *The Publisher apologizes for any inconvenience this may cause.* ,