| First Author | Chen Y | Year | 2023 |
| Journal | Cell Biosci | Volume | 13 |
| Issue | 1 | Pages | 84 |
| PubMed ID | 37170317 | Mgi Jnum | J:338611 |
| Mgi Id | MGI:7513970 | Doi | 10.1186/s13578-023-01024-4 |
| Citation | Chen Y, et al. (2023) ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1. Cell Biosci 13(1):84 |
| abstractText | BACKGROUND: ISGylation is a post-translational protein modification that regulates many life activities, including immunomodulation, antiviral responses, and embryo implantation. The exact contribution of ISGylation to folliculogenesis remains largely undefined. RESULTS: Here, Isg15 knockout in mice causes hyperfertility along with sensitive ovarian responses to gonadotropin, such as increases in cumulus expansion and ovulation rate. Moreover, ISG15 represses the expression of ovulation-related genes in an ISGylation-dependent manner. Mechanistically, ISG15 binds to ADAMTS1 via the ISG15-conjugating system (UBA7, UBE2L6, and HERC6), ISGylating ADAMTS1 at the binding sites Lys309, Lys593, Lys597, and Lys602, resulting in ADAMTS1 degradation via a 20S proteasome-dependent pathway. CONCLUSION: Taken together, the present study demonstrates that covalent ISG15 conjugation produces a novel regulatory axis of ISG15-ADAMTS1 that enhances the degradation of ADAMTS1, thereby compromising ovulation and female fertility. |
