Redox Regulation of STAT1 and STAT3 Signaling

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Sep 29

PMID 32987855

Citations 61

Authors

Elena Butturini

Alessandra Carcereri de Prati

Sofia Mariotto

Affiliations

Soon will be listed here.

Abstract

STAT1 and STAT3 are nuclear transcription factors that regulate genes involved in cell cycle, cell survival and immune response. The cross-talk between these signaling pathways determines how cells integrate the environmental signals received ultimately translating them in transcriptional regulation of specific sets of genes. Despite being activated downstream of common cytokine and growth factors, STAT1 and STAT3 play essentially antagonistic roles and the disruption of their balance directs cells from survival to apoptotic cell death or from inflammatory to anti-inflammatory responses. Different mechanisms are proposed to explain this yin-yang relationship. Considering the redox aspect of STATs proteins, this review attempts to summarize the current knowledge of redox regulation of STAT1 and STAT3 signaling focusing the attention on the post-translational modifications that affect their activity.

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References

Xie Y, Kole S, Precht P, Pazin M, Bernier M . S-glutathionylation impairs signal transducer and activator of transcription 3 activation and signaling. Endocrinology. 2008; 150(3):1122-31. PMC: 2654735. DOI: 10.1210/en.2008-1241. View

Linossi E, Babon J, Hilton D, Nicholson S . Suppression of cytokine signaling: the SOCS perspective. Cytokine Growth Factor Rev. 2013; 24(3):241-8. PMC: 3816980. DOI: 10.1016/j.cytogfr.2013.03.005. View

Kim H, Baumann H . The carboxyl-terminal region of STAT3 controls gene induction by the mouse haptoglobin promoter. J Biol Chem. 1997; 272(23):14571-9. DOI: 10.1074/jbc.272.23.14571. View

Gorina R, Sanfeliu C, Galito A, Messeguer A, Planas A . Exposure of glia to pro-oxidant agents revealed selective Stat1 activation by H2O2 and Jak2-independent antioxidant features of the Jak2 inhibitor AG490. Glia. 2007; 55(13):1313-24. DOI: 10.1002/glia.20542. View

Qu Y, Oyan A, Liu R, Hua Y, Zhang J, Hovland R . Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling. Cancer Res. 2013; 73(23):7090-100. DOI: 10.1158/0008-5472.CAN-13-1560. View

Dasgupta M, Dermawan J, Willard B, Stark G . STAT3-driven transcription depends upon the dimethylation of K49 by EZH2. Proc Natl Acad Sci U S A. 2015; 112(13):3985-90. PMC: 4386339. DOI: 10.1073/pnas.1503152112. View

Hoeve J, Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M . Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002; 22(16):5662-8. PMC: 133976. DOI: 10.1128/MCB.22.16.5662-5668.2002. View

Hoey T, Schindler U . STAT structure and function in signaling. Curr Opin Genet Dev. 1998; 8(5):582-7. DOI: 10.1016/s0959-437x(98)80015-4. View

Butturini E, Carcereri de Prati A, Chiavegato G, Rigo A, Cavalieri E, Darra E . Mild oxidative stress induces S-glutathionylation of STAT3 and enhances chemosensitivity of tumoural cells to chemotherapeutic drugs. Free Radic Biol Med. 2013; 65:1322-1330. DOI: 10.1016/j.freeradbiomed.2013.09.015. View

10.

Lim C, Cao X . Structure, function, and regulation of STAT proteins. Mol Biosyst. 2007; 2(11):536-50. DOI: 10.1039/b606246f. View

11.

Zhuang S . Regulation of STAT signaling by acetylation. Cell Signal. 2013; 25(9):1924-31. PMC: 4550442. DOI: 10.1016/j.cellsig.2013.05.007. View

12.

Butturini E, Gotte G, DellOrco D, Chiavegato G, Marino V, Canetti D . Intermolecular disulfide bond influences unphosphorylated STAT3 dimerization and function. Biochem J. 2016; 473(19):3205-19. DOI: 10.1042/BCJ20160294. View

13.

Shahul H, Sarma S . The structure of the thioredoxin-triosephosphate isomerase complex provides insights into the reversible glutathione-mediated regulation of triosephosphate isomerase. Biochemistry. 2011; 51(1):533-44. DOI: 10.1021/bi201224s. View

14.

Neculai D, Neculai A, Verrier S, Straub K, Klumpp K, Pfitzner E . Structure of the unphosphorylated STAT5a dimer. J Biol Chem. 2005; 280(49):40782-7. DOI: 10.1074/jbc.M507682200. View

15.

Veeriah S, Brennan C, Meng S, Singh B, Fagin J, Solit D . The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A. 2009; 106(23):9435-40. PMC: 2687998. DOI: 10.1073/pnas.0900571106. View

16.

Grohmann M, Wiede F, Dodd G, Gurzov E, Ooi G, Butt T . Obesity Drives STAT-1-Dependent NASH and STAT-3-Dependent HCC. Cell. 2018; 175(5):1289-1306.e20. PMC: 6242467. DOI: 10.1016/j.cell.2018.09.053. View

17.

Zgheib C, Kurdi M, Zouein F, Gunter B, Stanley B, Zgheib J . Acyloxy nitroso compounds inhibit LIF signaling in endothelial cells and cardiac myocytes: evidence that STAT3 signaling is redox-sensitive. PLoS One. 2012; 7(8):e43313. PMC: 3419695. DOI: 10.1371/journal.pone.0043313. View

18.

Reich N . STATs get their move on. JAKSTAT. 2014; 2(4):e27080. PMC: 3891633. DOI: 10.4161/jkst.27080. View

19.

Yu H, Zhi J, Cui Y, Tang E, Sun S, Feng J . Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells. Apoptosis. 2006; 11(6):931-41. DOI: 10.1007/s10495-006-6578-9. View

20.

Butturini E, Cavalieri E, Carcereri de Prati A, Darra E, Rigo A, Shoji K . Two naturally occurring terpenes, dehydrocostuslactone and costunolide, decrease intracellular GSH content and inhibit STAT3 activation. PLoS One. 2011; 6(5):e20174. PMC: 3097233. DOI: 10.1371/journal.pone.0020174. View