An alternatively transcribed TAZ variant negatively regulates JAK-STAT signaling

Chuantao Fang; Jian Li; Sixian Qi; Yubin Lei; Yan Zeng; Pengcheng Yu; Zhaolan Hu; Yufeng Zhou; Yulong Wang; Ruping Dai; Jin Li; Shenglin Huang; Pinglong Xu; Kang Chen; Chen Ding; Fa-Xing Yu

doi:10.15252/embr.201847227

An alternatively transcribed TAZ variant negatively regulates JAK-STAT signaling

EMBO Rep. 2019 Jun;20(6):e47227. doi: 10.15252/embr.201847227. Epub 2019 Apr 11.

Authors

Chuantao Fang¹, Jian Li¹, Sixian Qi¹, Yubin Lei¹, Yan Zeng¹, Pengcheng Yu^{2

3}, Zhaolan Hu⁴, Yufeng Zhou¹, Yulong Wang^{2

3}, Ruping Dai⁴, Jin Li¹, Shenglin Huang⁵, Pinglong Xu⁶, Kang Chen^{7

8

9}, Chen Ding¹⁰, Fa-Xing Yu¹¹

Affiliations

¹ Children's Hospital and Institutes of Biomedical Sciences, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China.
² Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China.
⁵ Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
⁷ Perinatology Research Branch, Eunice Kennedy Shriver NICHD, National Institutes of Health, Detroit, MI, USA.
⁸ Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
⁹ Jiangsu Province Hospital of TCM, The Affiliated Hospital of Nanjing University of TCM, Nanjing, China.
¹⁰ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
¹¹ Children's Hospital and Institutes of Biomedical Sciences, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China fxyu@fudan.edu.cn.

Abstract

Type I interferon (IFN)-induced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling drives the expression of IFN-stimulated genes (ISGs) to mediate antiviral response. The strength and duration of JAK-STAT signaling are tightly regulated to ensure effective antiviral defense while avoiding pathological inflammation and autoimmunity. Here, we report that cTAZ, an isoform of the Hippo pathway effector TAZ, is transcribed by an alternative promoter. Although majority of C-terminal sequences of TAZ is retained, cTAZ is not regulated by the Hippo signaling and does not mediate its growth-inhibitory functions. Instead, cTAZ negatively regulates JAK-STAT signaling by inhibiting STAT1/2 nuclear localization and ISG expression, and its expression is induced by type I IFN Thus, cTAZ functions as a modulator of JAK-STAT signaling and may play a role in fine-tuning cellular antiviral response.

Keywords: Hippo pathway; JAK‐STAT pathway; alternative transcript; viral infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gene Expression Profiling
Hippo Signaling Pathway
Humans
Janus Kinases / metabolism*
Mice
Models, Biological
Phosphorylation
Promoter Regions, Genetic*
Protein Binding
Protein Multimerization
Protein Serine-Threonine Kinases / metabolism
Protein Transport
RNA Isoforms
STAT Transcription Factors / chemistry
STAT Transcription Factors / metabolism*
Signal Transduction*
Trans-Activators / genetics*
Transcription, Genetic*
Transcriptional Coactivator with PDZ-Binding Motif Proteins

Substances

RNA Isoforms
STAT Transcription Factors
Trans-Activators
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human
Janus Kinases
Protein Serine-Threonine Kinases