Protein ISGylation: a Posttranslational Modification with Implications for Malignant Neoplasms

Overview

Journal Explor Target Antitumor Ther

Specialty Oncology

Date 2023 Sep 15

PMID 37711589

Authors

Angeles C Tecalco-Cruz

Jesus Zepeda-Cervantes

Affiliations

Soon will be listed here.

Abstract

Interferon (IFN)-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (UBL) protein family that can modify specific proteins via a catalytic process called ISGylation. This posttranslational modification can modulate the stability of the ISGylated proteins and protein-protein interactions. Some proteins modified by ISG15 have been identified in malignant neoplasms, suggesting the functional relevance of ISGylation in cancer. This review discusses the ISGylated proteins reported in malignant neoplasms that suggest the potential of ISG15 as a biomarker and therapeutic target in cancer.

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References

Wan X, Chen H, Khan M, Xu A, Yang F, Zhang Y . ISG15 inhibits IFN-α-resistant liver cancer cell growth. Biomed Res Int. 2013; 2013:570909. PMC: 3762208. DOI: 10.1155/2013/570909. View

Bolado-Carrancio A, Lee M, Ewing A, Muir M, Macleod K, Gallagher W . ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling. Oncogene. 2021; 40(44):6235-6247. PMC: 8566238. DOI: 10.1038/s41388-021-02017-8. View

DCunha J, Ramanujam S, WAGNER R, Witt P, KNIGHT Jr E, Borden E . In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996; 157(9):4100-8. View

Mustachio L, Kawakami M, Lu Y, Rodriguez-Canales J, Mino B, Behrens C . The ISG15-specific protease USP18 regulates stability of PTEN. Oncotarget. 2016; 8(1):3-14. PMC: 5352120. DOI: 10.18632/oncotarget.13914. View

Huang Y, Bulavin D . Oncogene-mediated regulation of p53 ISGylation and functions. Oncotarget. 2014; 5(14):5808-18. PMC: 4170631. DOI: 10.18632/oncotarget.2199. View

DCunha J, KNIGHT Jr E, Haas A, Truitt R, Borden E . Immunoregulatory properties of ISG15, an interferon-induced cytokine. Proc Natl Acad Sci U S A. 1996; 93(1):211-5. PMC: 40208. DOI: 10.1073/pnas.93.1.211. View

Yang E, Huang S, Jami-Alahmadi Y, McInerney G, Wohlschlegel J, Li M . Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes. PLoS Pathog. 2022; 18(9):e1010743. PMC: 9481182. DOI: 10.1371/journal.ppat.1010743. View

Daza-Cajigal V, Albuquerque A, Young D, Ciancanelli M, Moulding D, Angulo I . Partial human Janus kinase 1 deficiency predominantly impairs responses to interferon gamma and intracellular control of mycobacteria. Front Immunol. 2022; 13:888427. PMC: 9501714. DOI: 10.3389/fimmu.2022.888427. View

Wang B, Li Y, Wang H, Zhao J, Zhao Y, Liu Z . FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression. J Investig Med. 2019; 68(3):786-791. PMC: 7057795. DOI: 10.1136/jim-2019-001145. View

10.

Burks J, Reed R, Desai S . Free ISG15 triggers an antitumor immune response against breast cancer: a new perspective. Oncotarget. 2015; 6(9):7221-31. PMC: 4466680. DOI: 10.18632/oncotarget.3372. View

11.

Lertsooksawat W, Wongnoppavich A, Chairatvit K . Up-regulation of interferon-stimulated gene 15 and its conjugation machinery, UbE1L and UbcH8 expression by tumor necrosis factor-α through p38 MAPK and JNK signaling pathways in human lung carcinoma. Mol Cell Biochem. 2019; 462(1-2):51-59. DOI: 10.1007/s11010-019-03609-5. View

12.

Ganesan M, Poluektova L, Tuma D, Kharbanda K, Osna N . Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus-Infected Liver Cells by Up-Regulating USP18. Alcohol Clin Exp Res. 2016; 40(11):2329-2338. PMC: 6800117. DOI: 10.1111/acer.13226. View

13.

Edwards J, Delabat S, Badilla A, DiCaprio R, Hyun J, Burgess R . Downregulation of SOCS1 increases interferon-induced ISGylation during differentiation of induced-pluripotent stem cells to hepatocytes. JHEP Rep. 2022; 4(12):100592. PMC: 9685392. DOI: 10.1016/j.jhepr.2022.100592. View

14.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

15.

Wong J, Pung Y, Sze N, Chin K . HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006; 103(28):10735-40. PMC: 1484417. DOI: 10.1073/pnas.0600397103. View

16.

Spinnenhirn V, Bitzer A, Aichem A, Groettrup M . Newly translated proteins are substrates for ubiquitin, ISG15, and FAT10. FEBS Lett. 2016; 591(1):186-195. DOI: 10.1002/1873-3468.12512. View

17.

Singh P, Rai A, Verma A, Alsahli M, Rahmani A, Almatroodi S . Survival-Based Biomarker Module Identification Associated with Oral Squamous Cell Carcinoma (OSCC). Biology (Basel). 2021; 10(8). PMC: 8389591. DOI: 10.3390/biology10080760. View

18.

Ayub S, Kaul D . miR-2909 regulates ISGylation system via STAT1 signalling through negative regulation of SOCS3 in prostate cancer. Andrology. 2017; 5(4):790-797. DOI: 10.1111/andr.12374. View

19.

Vuillier F, Li Z, Commere P, Dynesen L, Pellegrini S . USP18 and ISG15 coordinately impact on SKP2 and cell cycle progression. Sci Rep. 2019; 9(1):4066. PMC: 6411882. DOI: 10.1038/s41598-019-39343-7. View

20.

Guo Y, Dolinko A, Chinyengetere F, Stanton B, Bomberger J, Demidenko E . Blockade of the ubiquitin protease UBP43 destabilizes transcription factor PML/RARα and inhibits the growth of acute promyelocytic leukemia. Cancer Res. 2010; 70(23):9875-85. PMC: 2999664. DOI: 10.1158/0008-5472.CAN-10-1100. View