Publications by authors named "E Jaffray"
Acute Promyelocytic Leukemia is caused by expression of the oncogenic Promyelocytic Leukemia (PML)-Retinoic Acid Receptor Alpha (RARA) fusion protein. Therapy with arsenic trioxide results in degradation of PML-RARA and PML and cures the disease. Modification of PML and PML-RARA with SUMO and ubiquitin precedes ubiquitin-mediated proteolysis.
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- The human genome comprises around 600 ubiquitin E3 ligases, with many being single-subunit E3s (ssE3s) that interact with both substrates and ubiquitin-loaded E2 enzymes.
- RNF4, a specific ssE3 ligase, features a disordered N-terminal region with SIMs crucial for binding SUMO-modified substrates, while maintaining a compact structure despite lacking secondary structure.
- Findings demonstrate that distinct charged regions in RNF4's N-terminus facilitate its proper configuration, essential for efficient substrate ubiquitination, and mutations that alter this shape reduce its activity.
Article Synopsis
- Oocyte meiotic spindles in many species operate without centrosomes, and understanding how chromosomes are accurately segregated in these spindles is still unclear.
- CLS-2, a protein similar to mammalian CLASP, is crucial for exerting forces on chromosomes during this process, while BUB-1, a checkpoint kinase, shows dynamic localization during anaphase.
- The study reveals that BUB-1 localization is regulated by SUMO modifications controlled by the SUMO E3 ligase GEI-17 and protease ULP-1, indicating a new SUMO-mediated regulatory mechanism affecting protein dynamics in early anaphase I of oocyte development.
During Caenorhabditis elegans oocyte meiosis, a multi-protein ring complex (RC) localized between homologous chromosomes, promotes chromosome congression through the action of the chromokinesin KLP-19. While some RC components are known, the mechanism of RC assembly has remained obscure. We show that SUMO E3 ligase GEI-17/PIAS is required for KLP-19 recruitment to the RC, and proteomic analysis identified KLP-19 as a SUMO substrate in vivo.
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- SUMO and ubiquitin are crucial for how cells respond to DNA damage, with Rnf4 acting as a link between these two processes.
- Rnf4 transfers ubiquitin to substrates modified by SUMO and can interact with various E2 enzymes, like Ube2w.
- In chicken and human cells, Rnf4 depletion increases sensitivity to DNA-damaging agents, while removing Ube2w alone doesn’t affect this response; however, Ube2w becomes harmful without Rnf4, suggesting they operate in separate pathways during DNA damage response.