| Substrate name | Substrate type/function | Biological process regulated by COP1-mediated turnover | Evidence source (citation information) | Year |
|---|---|---|---|---|
| p53 (TP53) | Tumor suppressor transcription factor | Stress responses, cell-cycle arrest, apoptosis, tumor suppression; COP1-mediated ubiquitination/degradation reduces p53 stability | First mammalian COP1 substrate discussed in structural review; p53 described as a COP1 target whose disruption stabilizes p53 (pqac-00000003, pqac-00000007, pqac-00000009) | 2023, 2024, 2026 |
| c-JUN | AP-1 family transcription factor | Cell proliferation, differentiation, survival; rapidly degraded after ERK1/2 inactivation via COP1 | CRL4^COP1/DET1 and COP1-dependent c-JUN degradation described in mechanistic and structural studies (pqac-00000003, pqac-00000011) | 2020, 2026 |
| ETV1 | ETS family transcription factor | Developmental and oncogenic transcriptional programs; COP1 promotes degradation | Listed among established COP1 substrates in mammalian cells (pqac-00000000, pqac-00000003) | 2020, 2026 |
| ETV4 | ETS family transcription factor | Mitogen-responsive transcription, proliferation, cancer-associated programs; COP1-dependent degradation, especially after ERK1/2 inactivation | Listed as CRL4^COP1/DET1 substrate and experimentally restored by COP1 knockdown (pqac-00000000, pqac-00000011) | 2020 |
| ETV5 | ETS family transcription factor | Mitogen-responsive transcription, proliferation, cancer-associated programs; COP1-dependent degradation | Listed as CRL4^COP1/DET1 substrate and experimentally restored by COP1 knockdown (pqac-00000000, pqac-00000011) | 2020 |
| ETS1 | ETS family transcription factor | Immune/developmental transcription programs and oncogenic signaling; COP1-mediated turnover | Named among COP1 substrates in review/mechanistic discussion (pqac-00000000, pqac-00000004) | 2020, 2021 |
| ETS2 | ETS family transcription factor | Developmental signaling and oncogenic transcriptional regulation; recognized by COP1 WD40 substrate-binding interface | Named among COP1 substrates and used as substrate in structural work (pqac-00000000, pqac-00000001, pqac-00000003) | 2020, 2026 |
| c/EBPβ (CEBPB) | CCAAT/enhancer-binding transcription factor | Microglial inflammatory state, neuroinflammation, complement-dependent neurotoxicity; COP1 suppresses its accumulation | Direct biochemical and functional evidence showing COP1 promotes proteasomal degradation of c/EBPβ (pqac-00000000, pqac-00000008) | 2020 |
| c/EBPα (CEBPA) | CCAAT/enhancer-binding transcription factor | Myeloid differentiation and growth control; known COP1 substrate via adaptor-mediated recruitment | Listed as established COP1 substrate in mammalian cells (pqac-00000000, pqac-00000010) | 2020, 2026 |
| UTX (KDM6A) | H3K27me2/3 histone demethylase; tumor suppressor | Chromatin regulation and colorectal tumor suppression; COP1-containing CRL4 complex promotes degradation, lowering UTX and favoring CRC progression | CRC study identifies CUL4B-DDB1-COP1 as functional E3 ligase for UTX degradation (pqac-00000005) | 2023 |
| P57Kip2 (CDKN1C) | Cyclin-dependent kinase inhibitor | Trophoblast cell-cycle exit and syncytiotrophoblast fusion; COP1-mediated degradation inhibits trophoblast fusion | STK40-dependent recruitment to COP1 reported in placental/trophoblast study (pqac-00000001) | 2024 |
| ACSL4 | Acyl-CoA synthetase involved in lipid metabolism and ferroptosis sensitivity | Ferroptosis control in renal cell carcinoma; COP1-mediated K48-linked ubiquitination reduces ACSL4 and suppresses ferroptosis | RCC study identifies ACSL4 as direct COP1 substrate (pqac-00000001) | 2025 |
| LUZP1 | Leucine zipper protein 1; cytoskeletal/signaling-associated protein | Colorectal cancer liver metastasis and oxaliplatin resistance; COP1-mediated degradation activates downstream MYL9 phosphorylation and EMT/JAK2-STAT3 signaling | Multi-omics organoid study identifies COP1-LUZP1 axis (pqac-00000001) | 2026 |
| c/EBP family/Tribbles-recruited substrates (general) | Transcription factors recruited by pseudokinase adaptors such as STK40/TRIB proteins | Signal-dependent repression of differentiation or inflammatory programs through adaptor-assisted COP1 targeting | Structural and functional studies indicate COP1 substrate recognition via WD40 domain and adaptor-assisted recruitment (pqac-00000003, pqac-00000008, pqac-00000010) | 2020, 2026 |


*Table: This table summarizes human COP1/RFWD2 substrates identified or discussed in the collected literature, including their functions and the biological processes affected by COP1-mediated degradation. It is useful for organizing the functional annotation of COP1 around its substrate repertoire and pathway roles.*