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An alternatively transcribed TAZ variant negatively regulates JAK-STAT signaling

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 ISGs 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.

SUBMITTER: Dr. Chuantao FANG

PROVIDER: S-SCDT-EMBOR-2018-47227V1 | biostudies-other |

REPOSITORIES: biostudies-other

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

Project description: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.

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