USP12 translocation maintains interferon antiviral efficacy by inhibiting CBP acetyltransferase activity

Autoři: Jin Liu aff001;  Lincong Jin aff001;  Xiangjie Chen aff001;  Yukang Yuan aff001;  Yibo Zuo aff001;  Ying Miao aff001;  Qian Feng aff001;  Hongguang Zhang aff001;  Fan Huang aff001;  Tingting Guo aff001;  Liting Zhang aff001;  Li Zhu aff003;  Feng Qian aff003;  Chuanwu Zhu aff003;  Hui Zheng aff001
Působiště autorů: International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China aff001;  Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China aff002;  The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China aff003
Vyšlo v časopise: USP12 translocation maintains interferon antiviral efficacy by inhibiting CBP acetyltransferase activity. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008215
Kategorie: Research Article


CREB-binding protein (CBP) participates in numerous transcription events. However, cell-intrinsic inhibitors of CBP are poorly defined. Here, we found that cellular USP12 interacts with the HAT domain of CBP and inhibits CBP’s acetyltransferase activity. Interestingly, USP12 positively regulates interferon (IFN) antiviral signaling independently of its deubiquitinase activity. Furthermore, we found that in IFN signaling USP12 translocates from the cytoplasm to the nucleus. The decrease in cytoplasmic USP12 facilitates CBP-induced acetylation and activation of IFN signaling proteins in the cytoplasm. Moreover, USP12 accumulation in the nucleus blocks CBP-induced acetylation of phosphorylated STAT1 (p-STAT1) and therefore inhibits the dephosphorylation effects of TCPTP on p-STAT1, which finally maintains nuclear p-STAT1 levels and IFN antiviral efficacy. USP12 nuclear translocation extends our understanding of the regulation of the strength of IFN antiviral signaling. Our study uncovers a cell-intrinsic regulation of CBP acetyltransferase activity and may provide potential strategies for IFN-based antiviral therapy.

Klíčová slova:

Acetylation – Antiviral immune response – Cytoplasm – Immunoprecipitation – Interferons – Small interfering RNAs – Vesicular stomatitis virus – TCR signaling cascade


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