| First Author | Yoshida A | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 10 | Pages | 1750-60 |
| PubMed ID | 23884858 | Mgi Jnum | J:385187 |
| Mgi Id | MGI:8331051 | Doi | 10.1182/blood-2012-12-476101 |
| Citation | Yoshida A, et al. (2013) COP1 targets C/EBPalpha for degradation and induces acute myeloid leukemia via Trib1. Blood 122(10):1750-60 |
| abstractText | The ubiquitin ligase constitutively photomorphogenic 1 (COP1) is involved in many biological responses in mammalian cells, but its role in tumorigenesis remains unclear. Here we show that COP1 is a ubiquitin ligase for the tumor suppressor CCAAT/enhancer-binding protein (C/EBPalpha) and promotes its degradation in vivo, thereby blocking myeloid differentiation of hematopoietic cells for tumorigenesis. In this process, mammalian homolog of Tribbles, Trib1, which contains a COP1-binding motif, is essential for down-regulation of C/EBPalpha expression. Murine bone marrow transplantation experiments showed that coexpression of COP1 accelerates development of acute myeloid leukemia induced by Trib1, which pathologically resembles that of p42C/EBPalpha-deficient mice. Interestingly, coexpression of ligase activity-deficient COP1 mutant abrogated Trib1-induced leukemogenesis. These results indicate that COP1 and Trib1 act as an oncoprotein complex functioning upstream of C/EBPalpha, and its ligase activity is crucial for leukemogenesis. |
