Protein Inhibitor of Activated STAT (PIAS) Negatively Regulates the JAK/STAT Pathway by Inhibiting STAT Phosphorylation and Translocation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 Nov 13

PMID 30416501

Citations 30

Authors

Guo-Juan Niu

Ji-Dong Xu

Wen-Jie Yuan

Jie-Jie Sun

Ming-Chong Yang

Zhong-Hua He

Xiao-Fan Zhao

Jin-Xing Wang

Affiliations

Soon will be listed here.

Abstract

Protein inhibitor of activated STAT (PIAS) proteins are activation-suppressing proteins for signal transducer and activator of transcription (STAT), which involves gene transcriptional regulation. The inhibitory mechanism of PIAS proteins in the Janus kinase (JAK)/STAT signaling pathway has been well studied in mammals and . However, the roles of PIAS in crustaceans are unclear. In the present study, we identified PIAS in kuruma shrimp and found that its relative expression could be induced by stimulation. To explore the function of PIAS in shrimp infected with , we performed an RNA interference assay. After knockdown of expression in shrimp subjected to infection, bacterial clearance was enhanced and the survival rate increased compared with those in the control shrimp ( injection). Simultaneously, the expression levels of antimicrobial peptides (AMPs), including anti-lipopolysaccharide factor (ALF) A1, C1, C2, and CruI-1, increased. Further study revealed that knockdown of also enhanced STAT phosphorylation and translocation. Pulldown assay indicated that PIAS interacts with activated STAT in shrimp. In conclusion, PIAS negatively regulates JAK/STAT signaling by inhibiting the phosphorylation and translocation of STAT through the interaction between PIAS and STAT, which leads to the reduction of AMP expression in shrimp. Our results revealed a new mechanism of PIAS-mediated gene regulation of the STAT signal pathway.

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References

Ke Y, Hunter M, Ng C, Perry M, Vandenberg J . Role of the cytoplasmic N-terminal Cap and Per-Arnt-Sim (PAS) domain in trafficking and stabilization of Kv11.1 channels. J Biol Chem. 2014; 289(20):13782-91. PMC: 4022852. DOI: 10.1074/jbc.M113.531277. View

Kotaja N, Karvonen U, Janne O, Palvimo J . PIAS proteins modulate transcription factors by functioning as SUMO-1 ligases. Mol Cell Biol. 2002; 22(14):5222-34. PMC: 139781. DOI: 10.1128/MCB.22.14.5222-5234.2002. View

Arora T, Liu B, He H, Kim J, Murphy T, Murphy K . PIASx is a transcriptional co-repressor of signal transducer and activator of transcription 4. J Biol Chem. 2003; 278(24):21327-30. DOI: 10.1074/jbc.C300119200. View

Jackson P . A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases. Genes Dev. 2001; 15(23):3053-8. DOI: 10.1101/gad.955501. View

Suzuki R, Shindo H, Tase A, Kikuchi Y, Shimizu M, Yamazaki T . Solution structures and DNA binding properties of the N-terminal SAP domains of SUMO E3 ligases from Saccharomyces cerevisiae and Oryza sativa. Proteins. 2008; 75(2):336-47. DOI: 10.1002/prot.22243. View

Di Napoli A, Jain P, Duranti E, Margolskee E, Arancio W, Facchetti F . Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway genes, TP53 and DNMT3A. Br J Haematol. 2016; 180(5):741-744. DOI: 10.1111/bjh.14431. View

Aravind L, Koonin E . SAP - a putative DNA-binding motif involved in chromosomal organization. Trends Biochem Sci. 2000; 25(3):112-4. DOI: 10.1016/s0968-0004(99)01537-6. View

Sun J, Lan J, Xu J, Niu G, Wang J . Suppressor of cytokine signaling 2 (SOCS2) negatively regulates the expression of antimicrobial peptides by affecting the Stat transcriptional activity in shrimp Marsupenaeus japonicus. Fish Shellfish Immunol. 2016; 56:473-482. DOI: 10.1016/j.fsi.2016.07.037. View

Nicolae A, Xi L, Pham T, Pham T, Navarro W, Meeker H . Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia. 2016; 30(11):2245-2247. PMC: 5093023. DOI: 10.1038/leu.2016.178. View

10.

Hari K, Cook K, Karpen G . The Drosophila Su(var)2-10 locus regulates chromosome structure and function and encodes a member of the PIAS protein family. Genes Dev. 2001; 15(11):1334-48. PMC: 312712. DOI: 10.1101/gad.877901. View

11.

Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R . PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 2001; 15(23):3088-103. PMC: 312834. DOI: 10.1101/gad.944801. View

12.

Shuai K . Regulation of cytokine signaling pathways by PIAS proteins. Cell Res. 2006; 16(2):196-202. DOI: 10.1038/sj.cr.7310027. View

13.

Liao J, Fu Y, Shuai K . Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction. Proc Natl Acad Sci U S A. 2000; 97(10):5267-72. PMC: 25817. DOI: 10.1073/pnas.97.10.5267. View

14.

Liu B, Liao J, Rao X, Kushner S, Chung C, Chang D . Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci U S A. 1998; 95(18):10626-31. PMC: 27945. DOI: 10.1073/pnas.95.18.10626. View

15.

Tolkunova E, Malashicheva A, Parfenov V, Sustmann C, Grosschedl R, Tomilin A . PIAS proteins as repressors of Oct4 function. J Mol Biol. 2007; 374(5):1200-12. DOI: 10.1016/j.jmb.2007.09.081. View

16.

Rytinki M, Kaikkonen S, Pehkonen P, Jaaskelainen T, Palvimo J . PIAS proteins: pleiotropic interactors associated with SUMO. Cell Mol Life Sci. 2009; 66(18):3029-41. PMC: 11115825. DOI: 10.1007/s00018-009-0061-z. View

17.

Sun J, Lan J, Zhao X, Vasta G, Wang J . Binding of a C-type lectin's coiled-coil domain to the Domeless receptor directly activates the JAK/STAT pathway in the shrimp immune response to bacterial infection. PLoS Pathog. 2017; 13(9):e1006626. PMC: 5645147. DOI: 10.1371/journal.ppat.1006626. View

18.

Li R, Pan Y, Shi D, Zhang Y, Zhang J . PIAS1 negatively modulates virus triggered type I IFN signaling by blocking the DNA binding activity of IRF3. Antiviral Res. 2013; 100(2):546-54. DOI: 10.1016/j.antiviral.2013.09.001. View

19.

Bao C, Li Y, Huan L, Zhang Y, Zhao F, Wang Q . NF-κB signaling relieves negative regulation by miR-194 in hepatocellular carcinoma by suppressing the transcription factor HNF-1α. Sci Signal. 2015; 8(387):ra75. DOI: 10.1126/scisignal.aaa8441. View

20.

Chung C, Liao J, Liu B, Rao X, Jay P, Berta P . Specific inhibition of Stat3 signal transduction by PIAS3. Science. 1997; 278(5344):1803-5. DOI: 10.1126/science.278.5344.1803. View