Molecular pathways that modulate ISG15/ISGylation levels in a cancer context
| Molecular pathway | Elements related to the ISGylation system | Effect | Cellular context | Reference |
|---|---|---|---|---|
| TNF-α, p38, and MAPK/JNK | ISG15 UBA7 UBE2L6 Protein ISGylation | Up | A549 (lung cancer) and HSC4 (human OSCC) cell lines | [90, 91] |
| Androgens | ISG15 Protein ISGylation | Down | Prostate cancer cells (LNCaP cell line) | [92] |
| Integrins (α5β1 and αV) through MRTF-A/SRF | ISG15 | Up | MDA-MB-231 breast cancer cell line | [93] |
| KLF9 | ISG15 | Down | HT29 CRC cells and a mouse model of CRC | [94] |
| RA | ISG15 UBA7 USP18 | Up | RA-sensitive leukemia cells | [95] |
| CYP1B1 | ISG15 HERC5 | Down | Hela cells | [28] |
| UV | ISG15 UBEA7 UBE2L6 ISGylation of PCNA | Up | Hela cells | [24] |
| DNA damage | ISG15 UBA7 UBE2L6 TRIM25 | Up | HEK293T, A549, and H1299 cell lines | [25] |
| Hypoxia | ISG15 ISGylation enzymes USP18 ISGylation of HIF-1α | Up | Human 769-P, Caki-1, and 293T renal cell lines | [26] |
| miR-138 | ISG15 mRNA | Down | Oral squamous carcinoma cells (CAL27 and SCC15 cells) | [96] |
| miR-370 | ISG15 mRNA | Down | Hepatocellular carcinoma cells | [97] |
| Inhibition of SOCS3 via miR-2909 | STAT1 ISG15 Protein ISGylation | Up | LNCaP prostate cancer cell line | [92] |
| BAG3 | ISG15 mRNA ISG15 protein | Down (mRNA) Up (protein) | PDACs | [98] |
| SOCS1 | STAT1 UBE2L6 Protein ISGylation | Down | iPSCs | [99] |
| WBSCR22 | ISG15 | Down | PC cells | [100] |
| Curcumin | Protein ISGylation | Down | MCF10A (human mammary tissue) and A549 (lung cancer) cells | [101] |
| KLF12 | ISG15 | Down | Cisplatin-resistant ovarian cancer cells | [81] |
TNF-α: tumor necrosis factor-α; MRTF-A: myocardin-related transcription factor A; SRF: serum response factor; KLF9: KLF transcription factor 9; RA: retinoic acid; CYP1B1: cytochrome P450 family 1 subfamily B member 1; miR-138: microRNA-138; SOCS3: suppressor of cytokine signaling 3; BAG3: BAG cochaperone 3; PDACs: PDA cells; iPSCs: induced pluripotent stem cells; WBSCR22: BUD23 rRNA methyltransferase and ribosome maturation factor; KLF12: KLF transcription factor 12; CRC: colorectal cancer