Table Info

Table 2.

Actions of free ISG15 in some cancer types

Cancer type	Actions	Reference
PDA	TAMS from patients with PDA exhibits a high ISG15 expression. TAM secretes ISG15, increasing the phenotype of CSCs. Moreover, IFN-β promotes that CSCs also secrete ISG15	[62]
Melanoma	Soluble ISG15 is secreted to medium from melanoma cells, promoting E–cadherin expression on human dendritic cells	[63]
ESCC	Patients with ESCC have increased ISG15 expression High levels of free ISG15 are found in the plasma of patients with ESCC compared with healthy patients	[64]
Breast cancer	Exogenous-free ISG15 reduces tumor growth in athymic mice by promoting NK cell infiltration Intracellular-free ISG15 promotes the expression of MHCI	[65]
OSCC	Free ISG15 interacts with Rac1-GDP, promoting cell migration in an ISGylation-independent manner. This event has been related to lymphatic metastasis of OSCC	[66]

PDA: pancreatic ductal adenocarcinoma; TAMs: tumor-associated macrophages; ESCC: esophageal squamous cell carcinoma; MHCI: major histocompatibility complex I; OSCC: oral squamous cell carcinoma; CSCs: cancer stem cells

Declarations

Acknowledgments

JZC thanks the Subprogram for the Incorporation of Young Career Academics (SIJA) from Dirección General de Asuntos del Personal Académico (DGAPA)-UNAM.

Author contributions

ACTC: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. JZC: Investigation, Validation, Writing—review & editing. Two authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was supported by the School of Science and Technology [CCyT-2022-08 to ACTC] from the Autonomous University of Mexico City (UACM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Knigth E Jr, Fahey D, Cordova B, Hillman M, Kutny R, Reich N, et al. A 15-kDa interferon-induced protein is derived by COOH-terminal processing of a 17-kDa precursor. J Biol Chem. 1988;263:4520–2. Erratum in: J Biol Chem. 1988;263;10040. [PubMed]

Potter JL, Narasimhan J, Mende-Mueller L, Haas AL. Precursor processing of pro-ISG15/UCRP, an interferon-β-induced ubiquitin-like protein. J Biol Chem. 1999;274:25061–8. [DOI] [PubMed]

Reich N, Evans B, Levy D, Fahey D, Knight E Jr, Darnell JE Jr. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. Proc Natl Acad Sci U S A. 1987;84:6394–8. [DOI] [PubMed] [PMC]

Narasimhan J, Wang M, Fu Z, Klein JM, Haas AL, Kim JJP. Crystal structure of the interferon-induced ubiquitin-like protein ISG15. J Biol Chem. 2005;280:27356–65. [DOI] [PubMed]

Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. J Biol Chem. 1992;267:7806–13. [PubMed]

Malakhov MP, Kim KI, Malakhova OA, Jacobs BS, Borden EC, Zhang DE. High-throughput immunoblotting: ubiquitin-like protein ISG15 modifies key regulators of signal transduction. J Biol Chem. 2003;278:16608–13. [DOI] [PubMed]

Tecalco-Cruz AC. Molecular pathways of interferon-stimulated gene 15: implications in cancer. Curr Protein Pept Sci. 2021;22:19–28. [DOI] [PubMed]

Mirzalieva O, Juncker M, Schwartzenburg J, Desai S. ISG15 and ISGylation in human diseases. Cells. 2022;11:538. [DOI] [PubMed] [PMC]

Malakhov MP, Malakhova OA, Kim KI, Ritchie KJ, Zhang DE. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 2002;277:9976–81. [DOI] [PubMed]

10.

Ketscher L, Hannß R, Moralese DJ, Basters A, Guerra S, Goldmann T, et al. Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance. Proc Natl Acad Sci U S A. 2015;112:1577–82. [DOI] [PubMed] [PMC]

11.

Ketscher L, Knobeloch KP. ISG15 uncut: dissecting enzymatic and non-enzymatic functions of USP18 in vivo. Cytokine. 2015;76:569–71. [DOI] [PubMed]

12.

Durfee LA, Lyon N, Seo K, Huibregtse JM. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Mol Cell. 2010;38:722–32. [DOI] [PubMed] [PMC]

13.

Spinnenhirn V, Bitzer A, Aichem A, Groettrup M. Newly translated proteins are substrates for ubiquitin, ISG15, and FAT10. FEBS Lett. 2017;591:186–95. [DOI] [PubMed]

14.

Huang YF, Wee S, Gunaratne J, Lane DP, Bulavin DV. Isg15 controls p53 stability and functions. Cell Cycle. 2014;13:2199–209. [DOI] [PubMed] [PMC]

15.

Xu D, Zhang T, Xiao J, Zhu K, Wei R, Wu Z, et al. Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon. Autophagy. 2015;11:617–28. [DOI] [PubMed] [PMC]

16.

Huang YF, Bulavin DV. Oncogene-mediated regulation of p53 ISGylation and functions. Oncotarget. 2014;5:5808–18. [DOI] [PubMed] [PMC]

17.

Zou W, Wang J, Zhang DE. Negative regulation of ISG15 E3 ligase EFP through its autoISGylation. Biochem Biophys Res Commun. 2007;354:321–7. [DOI] [PubMed] [PMC]

18.

Jeon YJ, Choi JS, Lee JY, Yu KR, Kim SM, Ka SH, et al. ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway. EMBO Rep. 2009;10:374–80. [DOI] [PubMed] [PMC]

19.

Im E, Yoo L, Hyun M, Shin WH, Chung KC. Covalent ISG15 conjugation positively regulates the ubiquitin E3 ligase activity of parkin. Open Biol. 2016;6:160193. [DOI] [PubMed] [PMC]

20.

Jeon YJ, Jo MG, Yoo HM, Hong SH, Park JM, Ka SH, et al. Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15. J Clin Invest. 2012;122:2622–36. [DOI] [PubMed] [PMC]

21.

Okumura F, Zou W, Zhang DE. ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP. Genes Dev. 2007;21:255–60. [DOI] [PubMed] [PMC]

22.

Zou W, Zhang DE. The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 ligase. J Biol Chem. 2006;281:3989–94. [DOI] [PubMed]

23.

Chen Z, Zheng L, Chen Y, Liu X, Kawakami M, Mustachio LM, et al. Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis. Cancer Biol Ther. 2022;23:265–80. [DOI] [PubMed] [PMC]

24.

Park JM, Yang SW, Yu KR, Ka SH, Lee SW, Seol JH, et al. Modification of PCNA by ISG15 plays a crucial role in termination of error-prone translesion DNA synthesis. Mol Cell. 2014;54:626–38. [DOI] [PubMed]

25.

Park JH, Yang SW, Park JM, Ka SH, Kim JH, Kong YY, et al. Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification. Nat Commun. 2016;7:12513. [DOI] [PubMed] [PMC]

26.

Yeh YH, Yang YC, Hsieh MY, Yeh YC, Li TK. A negative feedback of the HIF-1α pathway via interferon-stimulated gene 15 and ISGylation. Clin Cancer Res. 2013;19:5927–39. [DOI] [PubMed]

27.

Lee JH, Bae JA, Lee JH, Seo YW, Kho DH, Sun EG, et al. Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/β-catenin signal via ISGylation of β-catenin. Gut. 2010;59:907–17. [DOI] [PubMed]

28.

Park YS, Kwon YJ, Chun YJ. CYP1B1 activates Wnt/β-catenin signaling through suppression of Herc5-mediated ISGylation for protein degradation on β-catenin in HeLa cells. Toxicol Res. 2017;33:211–8. [DOI] [PubMed] [PMC]

29.

Wang B, Li Y, Wang H, Zhao J, Zhao Y, Liu Z, et al. FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression. J Investig Med. 2020;68:786–91. [DOI] [PubMed] [PMC]

30.

Mustachio LM, Kawakami M, Lu Y, Rodriguez-Canales J, Mino B, Behrens C, et al. The ISG15-specific protease USP18 regulates stability of PTEN. Oncotarget. 2017;8:3–14. [DOI] [PubMed] [PMC]

31.

Zhang C, Cui J, Cao L, Tian X, Miao Y, Wang Y, et al. ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma. J Cell Mol Med. 2022;26:5078–94. [DOI] [PubMed] [PMC]

32.

Xue X, Tian X, Zhang C, Miao Y, Wang Y, Peng Y, et al. YAP ISGylation increases its stability and promotes its positive regulation on PPP by stimulating 6PGL transcription. Cell Death Discov. 2022;8:59. [DOI] [PubMed] [PMC]

33.

Bolado-Carrancio A, Lee M, Ewing A, Muir M, Macleod KG, Gallagher WM, et al. ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling. Oncogene. 2021;40:6235–47. [DOI] [PubMed] [PMC]

34.

Dai Y, Yu T, Yu C, Lu T, Zhou L, Cheng C, et al. ISG15 enhances glioma cell stemness by promoting Oct4 protein stability. Environ Toxicol. 2022;37:2133–42. [DOI] [PubMed]

35.

Liu M, Li XL, Hassel BA. Proteasomes modulate conjugation to the ubiquitin-like protein, ISG15. J Biol Chem. 2003;278:1594–602. [DOI] [PubMed]

36.

Desai SD, Haas AL, Wood LM, Tsai YC, Pestka S, Rubin EH, et al. Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res. 2006;66:921–8. [DOI] [PubMed]

37.

Fan JB, Arimoto KI, Motamedchaboki K, Yan M, Wolf DA, Zhang DE. Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis. Sci Rep. 2015;5:12704. [DOI] [PubMed] [PMC]

38.

Ganesan M, Poluektova LY, Tuma DJ, Kharbanda KK, Osna NA. Acetaldehyde disrupts interferon alpha signaling in hepatitis C virus-infected liver cells by up-regulating USP18. Alcohol Clin Exp Res. 2016;40:2329–38. [DOI] [PubMed] [PMC]

39.

Wan X, Chen H, Khan MA, Xu A, Yang F, Zhang Y, et al. ISG15 inhibits IFN-α-resistant liver cancer cell growth. Biomed Res Int. 2013;2013:570909. [DOI] [PubMed] [PMC]

40.

Nakashima H, Nguyen T, Goins WF, Chiocca EA. Interferon-stimulated gene 15 (ISG15) and ISG15-linked proteins can associate with members of the selective autophagic process, histone deacetylase 6 (HDAC6) and SQSTM1/p62. J Biol Chem. 2015;290:1485–95. [DOI] [PubMed] [PMC]

41.

Villarroya-Beltri C, Baixauli F, Mittelbrunn M, Fernández-Delgado I, Torralba D, Moreno-Gonzalo O, et al. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun. 2016;7:13588. [DOI] [PubMed] [PMC]

42.

Burks J, Reed RE, Desai SD. ISGylation governs the oncogenic function of Ki-Ras in breast cancer. Oncogene. 2014;33:794–803. [DOI] [PubMed]

43.

Falvey CM, O’Donovan TR, El-Mashed S, Nyhan MJ, O’Reilly S, McKenna SL. UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells. Oncotarget. 2017;8:23479–91. Erratum in: Oncotarget. 2020;11:212. [DOI] [PubMed] [PMC]

44.

Cerikan B, Schiebel E. DOCK6 inactivation highlights ISGylation as RHO-GTPase balancer. Cell Cycle. 2017;16:304–5. [DOI] [PubMed] [PMC]

45.

Cerikan B, Shaheen R, Colo GP, Gläßer C, Hata S, Knobeloch KP, et al. Cell-intrinsic adaptation arising from chronic ablation of a key Rho GTPase regulator. Dev Cell. 2016;39:28–43. [DOI] [PubMed]

46.

Cruz-Ramos E, Macías-Silva M, Sandoval-Hernández A, Tecalco-Cruz AC. Non-muscle myosin IIA is post-translationally modified by interferon-stimulated gene 15 in breast cancer cells. Int J Biochem Cell Biol. 2019;107:14–26. [DOI] [PubMed]

47.

Takeuchi T, Yokosawa H. ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating activity. Biochem Biophys Res Commun. 2005;336:9–13. [DOI] [PubMed]

48.

Yoo L, Yoon AR, Yun CO, Chung KC. Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon. Cell Death Dis. 2018;9:97. [DOI] [PubMed] [PMC]

49.

Wardlaw CP, Petrini JHJ. ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress. Nat Commun. 2022;13:5971. [DOI] [PubMed] [PMC]

50.

Alcalá S, Sancho P, Martinelli P, Navarro D, Pedrero C, Martín-Hijano L, et al. ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity. Nat Commun. 2020;11:2682. [DOI] [PubMed] [PMC]

51.

Malakhova OA, Kim KI, Luo JK, Zou W, Kumar KGS, Fuchs SY, et al. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO Journal. 2006;25:2358–67. [DOI] [PubMed] [PMC]

52.

Rempel LA, Austin KJ, Ritchie KJ, Yan M, Shen M, Zhang DE, et al. Ubp43 gene expression is required for normal Isg15 expression and fetal development. Reprod Biol and Endocrinol. 2007;5:13. [DOI] [PubMed] [PMC]

53.

Ritchie KJ, Malakhov MP, Hetherington CJ, Zhou L, Little MT, Malakhova OA, et al. Dysregulation of protein modification by ISG15 results in brain cell injury. Genes Dev. 2002;16:2207–12. [DOI] [PubMed] [PMC]

54.

D’Cunha J, Knight E, Haas AL, Truitt RL, Borden EC. Immunoregulatory properties of ISG15, an interferon-induced cytokine. Proc Natl Acad Sci U S A. 1996;93:211–5. [DOI] [PubMed] [PMC]

55.

D’Cunha J, Ramanujam S, Wagner RJ, Witt PL, Knight E Jr, Borden EC. In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996;157:4100–8. [PubMed]

56.

Knight E Jr, Cordova B. IFN-induced 15-kDa protein is released from human lymphocytes and monocytes. J Immunol. 1991;146:2280–4. [PubMed]

57.

Daza-Cajigal V, Albuquerque AS, Young DF, Ciancanelli MJ, Moulding D, Angulo I, et al. Partial human Janus kinase 1 deficiency predominantly impairs responses to interferon gamma and intracellular control of mycobacteria. Front Immunol. 2022;13:888427. [DOI] [PubMed] [PMC]

58.

Fan JB, Zhang DE. ISG15 regulates IFN-γ immunity in human mycobacterial disease. Cell Res. 2013;23:173–5. [DOI] [PubMed] [PMC]

59.

Swaim CD, Scott AF, Canadeo LA, Huibregtse JM. Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor. Mol Cell. 2017;68:581–90.e5. [DOI] [PubMed] [PMC]

60.

Chen RH, Xiao ZW, Yan XQ, Han P, Liang FY, Wang JY, et al. Tumor cell-secreted ISG15 promotes tumor cell migration and immune suppression by inducing the macrophage M2-like phenotype. Front Immunol. 2020;11:594775. [DOI] [PubMed] [PMC]

61.

Tecalco-Cruz AC. ISG15 and ISGylation: emergence in the cytoskeleton dynamic and tumor microenvironment. BIOCELL. 2022;46:1209–13. [DOI]

62.

Sainz B Jr, Martín B, Tatari M, Heeschen C, Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 2014;74:7309–20. [DOI] [PubMed]

63.

Padovan E, Terracciano L, Certa U, Jacobs B, Reschner A, Bolli M, et al. Interferon stimulated gene 15 constitutively produced by melanoma cells induces E-cadherin expression on human dendritic cells. Cancer Res. 2002;62:3453–8. [PubMed]

64.

Yuan H, Zhou W, Yang Y, Xue L, Liu L, Song Y. ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway. Exp Cell Res. 2018;367:47–55. [DOI] [PubMed]

65.

Burks J, Reed RE, Desai SD. Free ISG15 triggers an antitumor immune response against breast cancer: a new perspective. Oncotarget. 2015;6:7221–31. [DOI] [PubMed] [PMC]

66.

Chen YL, Wu WL, Jang CW, Yen YC, Wang SH, Tsai FY, et al. Interferon-stimulated gene 15 modulates cell migration by interacting with Rac1 and contributes to lymph node metastasis of oral squamous cell carcinoma cells. Oncogene. 2019;38:4480–95. [DOI] [PubMed]

67.

Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, et al. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature. 2015;517:89–93. [DOI] [PubMed] [PMC]

68.

Vuillier F, Li Z, Commere PH, Dynesen LT, Pellegrini S. USP18 and ISG15 coordinately impact on SKP2 and cell cycle progression. Sci Rep. 2019;9:4066. [DOI] [PubMed] [PMC]

69.

Malakhova OA, Zhang DE. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response. J Biol Chem. 2008;283:8783–7. [DOI] [PubMed] [PMC]

70.

Du Y, Duan T, Feng Y, Liu Q, Lin M, Cui J, et al. LRRC25 inhibits type I IFN signaling by targeting ISG15‐associated RIG‐I for autophagic degradation. EMBO J. 2018;37:351–66. [DOI] [PubMed] [PMC]

71.

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:W98–102. [DOI] [PubMed] [PMC]

72.

Bektas N, Noetzel E, Veeck J, Press MF, Kristiansen G, Naami A, et al. The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer. Breast Cancer Res. 2008;10:R58. [DOI] [PubMed] [PMC]

73.

Tecalco-Cruz AC, Cortés-González CC, Cruz-Ramos E, Ramírez Jarquín JO, Romero-Mandujano AK, Sosa-Garrocho M. Interplay between interferon-stimulated gene 15/ISGylation and interferon gamma signaling in breast cancer cells. Cell Signal. 2019;54:91–101. [DOI] [PubMed]

74.

Chen RH, Du Y, Han P, Wang HB, Liang FY, Feng GK, et al. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma. Oncotarget. 2016;7:16910–22. [DOI] [PubMed] [PMC]

75.

Singh P, Rai A, Verma AK, Alsahli MA, Rahmani AH, Almatroodi SA, et al. Survival-based biomarker module identification associated with oral squamous cell carcinoma (OSCC). Biology (Basel). 2021;10:760. [DOI] [PubMed] [PMC]

76.

Chi LM, Lee CW, Chang KP, Hao SP, Lee HM, Liang Y, et al. Enhanced interferon signaling pathway in oral cancer revealed by quantitative proteome analysis of microdissected specimens using ¹⁶O/¹⁸O labeling and integrated two-dimensional LC-ESI-MALDI tandem MS. Mol Cell Proteomics. 2009;8:1453–74. [DOI] [PubMed] [PMC]

77.

Desai SD, Reed RE, Burks J, Wood LM, Pullikuth AK, Haas AL, et al. ISG15 disrupts cytoskeletal architecture and promotes motility in human breast cancer cells. Exp Biol Med (Maywood). 2012;237:38–49. [DOI] [PubMed]

78.

Tecalco-Cruz AC, Velasco-Loyden G, Robles-Villarruel L, Cortes-González CC, Zepeda-Cervantes J, Pineda B, et al. Interferon-stimulated gene 15 and ISGylation are upregulated in glioblastoma. Biochem Biophys Res Commun. 2022;621:144–50. [DOI] [PubMed]

79.

Yeung TL, Tsai C, Leung C, Au Yeung CL, Thompson M, Lu K, et al. ISG15 promotes ERK1 ISGylation, CD8+ T cell activation and suppresses ovarian cancer progression. Cancers (Basel). 2018;10:464. [DOI] [PubMed] [PMC]

80.

Mao H, Wang M, Cao B, Zhou H, Zhang Z, Mao X. Interferon-stimulated gene 15 induces cancer cell death by suppressing the NF-κB signaling pathway. Oncotarget. 2016;7:70143–51. [DOI] [PubMed] [PMC]

81.

Zhang Q, Wang J, Qiao H, Huyan L, Liu B, Li C, et al. ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell-like features in cisplatin-resistant ovarian cancer. J Cell Mol Med. 2021;25:4395–407. [DOI] [PubMed] [PMC]

82.

Tao P, Sun L, Sun Y, Wang Y, Yang Y, Yang B, et al. ISG15 is associated with cervical cancer development. Oncol Lett. 2022;24:380. [DOI] [PubMed] [PMC]

83.

Zhou MJ, Chen FZ, Chen HC, Wan XX, Zhou X, Fang Q, et al. ISG15 inhibits cancer cell growth and promotes apoptosis. Int J Mol Med. 2017;39:446–52. [DOI] [PubMed]

84.

Zhao X, Wang J, Yaojie Y, Zhang M, Zhao W, Zhang H, et al. Interferonstimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response. Oncol Rep. 2022;47:110. [DOI] [PubMed] [PMC]

85.

Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, et al. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev. 2003;17:455–60. [DOI] [PubMed] [PMC]

86.

Tecalco Cruz AC, Mejía-Barreto K. Cell type-dependent regulation of free ISG15 levels and ISGylation. J Cell Commun Signal. 2017;11:127–35. [DOI] [PubMed] [PMC]

87.

Dastur A, Beaudenon S, Kelley M, Krug RM, Huibregtse JM. Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells. J Biol Chem. 2006;281:4334–8. [DOI] [PubMed]

88.

Wong JJY, Pung YF, Sze NSK, Chin KC. 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;103:10735–40. [DOI] [PubMed] [PMC]

89.

Zhao C, Beaudenon SL, Kelley ML, Waddell MB, Yuan W, Schulman BA, et al. The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-α/β-induced ubiquitin-like protein. Proc Natl Acad Sci U S A. 2004;101:7578–82. [DOI] [PubMed] [PMC]

90.

Chairatvit K, Wongnoppavich A, Choonate S. Up-regulation of interferon-stimulated gene15 and its conjugates by tumor necrosis factor-α via type I interferon-dependent and -independent pathways. Mol Cell Biochem. 2012;368:195–201. [DOI] [PubMed]

91.

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;462:51–9. [DOI] [PubMed]

92.

Ayub SG, Kaul D. miR-2909 regulates ISGylation system via STAT1 signalling through negative regulation of SOCS3 in prostate cancer. Andrology. 2017;5:790–7. [DOI] [PubMed]

93.

Hermann MR, Jakobson M, Colo GP, Rognoni E, Jakobson M, Kupatt C, et al. Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion. J Cell Sci. 2016;129:1391–403. [DOI] [PubMed]

94.

Brown AR, Simmen RCM, Raj VR, Van TT, MacLeod SL, Simmen FA. Krüppel-like factor 9 (KLF9) prevents colorectal cancer through inhibition of interferon-related signaling. Carcinogenesis. 2015;36:946–55. [DOI] [PubMed] [PMC]

95.

Guo Y, Dolinko AV, Chinyengetere F, Stanton B, Bomberger JM, Demidenko E, et al. Blockade of the ubiquitin protease UBP43 destabilizes transcription factor PML/RARα and inhibits the growth of acute promyelocytic leukemia. Cancer Res. 2010;70:9875–85. [DOI] [PubMed] [PMC]

96.

Zhang Q, He Y, Nie M, Cai W. Roles of miR-138 and ISG15 in oral squamous cell carcinoma. Exp Ther Med. 2017;14:2329–34. [DOI] [PubMed] [PMC]

97.

Liu Z, Ma M, Yan L, Chen S, Li S, Yang D, et al. miR-370 regulates ISG15 expression and influences IFN-α sensitivity in hepatocellular carcinoma cells. Cancer Biomark. 2018;22:453–66. [DOI] [PubMed] [PMC]

98.

Li XY, Yan J, Sun J, Li C, Jiang JY, Wang JM, et al. BAG3 deletion suppresses stem cell-like features of pancreatic ductal adenocarcinoma via translational suppression of ISG15. Biochim Biophys Acta Mol Cell Res. 2019;1866:819–27. [DOI] [PubMed]

99.

Edwards JS, Delabat SA, Badilla AD, DiCaprio RC, Hyun J, Burgess RA, et al. Downregulation of SOCS1 increases interferon-induced ISGylation during differentiation of induced-pluripotent stem cells to hepatocytes. JHEP Reports. 2022;4:100592. [DOI] [PubMed] [PMC]

100.

Khan A, Huang H, Zhao Y, Li H, Pan R, Wang S, et al. WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15. Int J Oncol. 2022;60:24. [DOI] [PubMed] [PMC]

101.

Oki N, Yamada S, Tanaka T, Fukui H, Hatakeyama S, Okumura F. Curcumin partly prevents ISG15 activation via ubiquitin-activating enzyme E1-like protein and decreases ISGylation. Biochem Biophys Res Commun. 2022;625:94–101. [DOI] [PubMed] [PMC]

102.

Nyman TA, Matikainen S, Sareneva T, Julkunen I, Kalkkinen N. Proteome analysis reveals ubiquitin-conjugating enzymes to be a new family of interferon-α-regulated genes. Eur J Biochem. 2000;267:4011–9. [DOI] [PubMed]

103.

Serniwka SA, Shaw GS. The structure of the UbcH8−ubiquitin complex shows a unique ubiquitin interaction site. Biochemistry. 2009;48:12169–79. [DOI] [PubMed]

104.

Buchwald M, Pietschmann K, Müller JP, Böhmer FD, Heinzel T, Krämer OH. Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation. Leukemia. 2010;24:1412–21. [DOI] [PubMed]

105.

Yang E, Huang S, Jami-Alahmadi Y, McInerney GM, Wohlschlegel JA, Li MMH. Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes. PLoS Pathog. 2022;18:e1010743. [DOI] [PubMed] [PMC]

106.

Tecalco-Cruz AC, Abraham-Juárez MJ, Solleiro-Villavicencio H, Ramírez-Jarquín JO. TRIM25: a central factor in breast cancer. World J Clin Oncol. 2021;12:646–55. [DOI] [PubMed] [PMC]

107.

Nguyen HM, Gaikwad S, Oladejo M, Paulishak W, Wood LM. Targeting ubiquitin-like protein, ISG15, as a novel tumor associated antigen in colorectal cancer. Cancers (Basel). 2023;15:1237. [DOI] [PubMed] [PMC]

108.

Nguyen HM, Oladejo M, Paulishak W, Wood LM. A Listeria-based vaccine targeting ISG15 exerts anti-tumor efficacy in renal cell carcinoma. Cancer Immunol Immunother. 2022;72:2889–903. [DOI] [PubMed]

109.

Huo Y, Zong Z, Wang Q, Zhang Z, Deng H. ISG15 silencing increases cisplatin resistance via activating p53-mediated cell DNA repair. Oncotarget. 2017;8:107452–61. [DOI] [PubMed] [PMC]

110.

Wang JM, Liu BQ, Zhang Q, Hao L, Li C, Yan J, et al. ISG15 suppresses translation of ABCC2 via ISGylation of hnRNPA2B1 and enhances drug sensitivity in cisplatin resistant ovarian cancer cells. Biochim Biophys Acta Mol Cell Res. 2020;1867:118647. [DOI] [PubMed]

111.

Mondaza-Hernandez JL, Moura DS, Lopez-Alvarez M, Sanchez-Bustos P, Blanco-Alcaina E, Castilla-Ramirez C, et al. ISG15 as a prognostic biomarker in solitary fibrous tumour. Cell Mol Life Sci. 2022;79:434. [DOI] [PubMed] [PMC]

112.

Pinto-Fernandez A, Salio M, Partridge T, Chen J, Vere G, Greenwood H, et al. Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity. Br J Cancer. 2021;124:817–30. [DOI] [PubMed] [PMC]