RRC ID 54455
著者 Moreno-Moreno O, Torras-Llort M, Azorin F.
タイトル The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle.
ジャーナル 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.
巻・号 47(7)
ページ 3395-3406
公開日 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
引用数 4
リソース情報
ショウジョウバエ 9952R-2