Degradation of Human RAP80 is Cell Cycle Regulated by Cdc20 and Cdh1 Ubiquitin Ligases
Copyright policy )Degradation of Human RAP80 is Cell Cycle Regulated by Cdc20 and Cdh1 Ubiquitin Ligases
Abstract Receptor-associated protein 80 (RAP80) is a component of the BRCA1-A complex that recruits BRCA1 to DNA damage sites in the DNA damage–induced ubiquitin signaling pathway. RAP80-depleted cells showed defective G2–M phase checkpoint control. In this study, we show that RAP80 protein levels fluctuate during the cell cycle. Its expression level peaked in the G2 phase and declined during mitosis and progression into the G1 phase. Also, RAP80 is polyubiquitinated and degraded by the anaphase-promoting complex (APC/C)Cdc20 or (APC/C)Cdh1. Consistent with this, knockdown of Cdc20 or Cdh1 expression by transfecting with small interfering RNAs blocked RAP80 degradation during mitosis or the G1 phase, respectively. A conserved destruction box (D box) in RAP80 affected its stability and ubiquitination, which was dependent on APC/cyclosomeCdc20 (CCdc20) or APC/cyclosomeCdh1 (CCdh1). In addition, overexpression of RAP80 destruction box1 deletion mutant attenuated mitotic progression. Thus, APC/CCdc20 or APC/CCdh1 complexes regulate RAP80 stability during mitosis to the G1 phase, and these events are critical for a novel function of RAP80 in mitotic progression. Mol Cancer Res; 10(5); 615–25. ©2012 AACR.
- Sungkyunkwan University Korea (Republic of)
- Sookmyung Women's University Korea (Republic of)
- UNIST (Ulsan National Institute of Science and Technology) Korea (Republic of)
- Sungkyul University Korea (Republic of)
572, Cdc20 Proteins, Cell Cycle, G1 Phase, Ubiquitination, Mitosis, Nuclear Proteins, Cell Cycle Proteins, Cadherins, DNA-Binding Proteins, HEK293 Cells, Antigens, CD, Gene Knockdown Techniques, Proteolysis, Humans, Histone Chaperones, RNA, Small Interfering, Carrier Proteins, HeLa Cells, Sequence Deletion, Signal Transduction
572, Cdc20 Proteins, Cell Cycle, G1 Phase, Ubiquitination, Mitosis, Nuclear Proteins, Cell Cycle Proteins, Cadherins, DNA-Binding Proteins, HEK293 Cells, Antigens, CD, Gene Knockdown Techniques, Proteolysis, Humans, Histone Chaperones, RNA, Small Interfering, Carrier Proteins, HeLa Cells, Sequence Deletion, Signal Transduction
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