Reference - Detail
| RRC ID | 54455 |
|---|---|
| Author | Moreno-Moreno O, Torras-Llort M, Azorin F. |
| Title | The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle. |
| Journal | Nucleic Acids Res |
| Abstract |
Centromere identity is determined by the specific deposition of CENP-A, a histone H3 variant localizing exclusively at centromeres. Increased CENP-A expression, which is a frequent event in cancer, causes mislocalization, ectopic kinetochore assembly and genomic instability. Proteolysis regulates CENP-A expression and prevents its misincorporation across chromatin. How proteolysis restricts CENP-A localization to centromeres is not well understood. Here we report that, in Drosophila, CENP-ACID expression levels are regulated throughout the cell cycle by the combined action of SCFPpa and APC/CCdh1. We show that SCFPpa regulates CENP-ACID expression in G1 and, importantly, in S-phase preventing its promiscuous incorporation across chromatin during replication. In G1, CENP-ACID expression is also regulated by APC/CCdh1. We also show that Cal1, the specific chaperone that deposits CENP-ACID at centromeres, protects CENP-ACID from SCFPpa-mediated degradation but not from APC/CCdh1-mediated degradation. These results suggest that, whereas SCFPpa targets the fraction of CENP-ACID that is not in complex with Cal1, APC/CCdh1 mediates also degradation of the Cal1-CENP-ACID complex and, thus, likely contributes to the regulation of centromeric CENP-ACID deposition. |
| Volume | 47(7) |
| Pages | 3395-3406 |
| Published | 2019-4-23 |
| DOI | 10.1093/nar/gkz060 |
| PII | 5310037 |
| PMID | 30753559 |
| PMC | PMC6468245 |
| MeSH | Anaphase-Promoting Complex-Cyclosome / metabolism* Animals Cdh1 Proteins / metabolism* Cell Cycle* Cell Line Centromere / metabolism Centromere Protein A / metabolism* Drosophila Proteins / metabolism Drosophila melanogaster / cytology* Drosophila melanogaster / enzymology Drosophila melanogaster / metabolism* G1 Phase S Phase Ubiquitin-Protein Ligases / metabolism* |
| IF | 11.147 |
| Times Cited | 4 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | 9952R-2 |