Format

Send to

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

An alternatively transcribed TAZ variant negatively regulates JAK-STAT signaling.

Fang C1, Li J1, Qi S1, Lei Y1, Zeng Y1, Yu P2,3, Hu Z4, Zhou Y1, Wang Y2,3, Dai R4, Li J1, Huang S5, Xu P6, Chen K7,8,9, Ding C10, Yu FX11.

Author information

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

PMID:
30979708
PMCID:
PMC6549033
[Available on 2020-06-01]
DOI:
10.15252/embr.201847227

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center