| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 10221 |
Name | TRIB1 |
Synonymous | tribbles pseudokinase 1;TRIB1;tribbles pseudokinase 1 |
Definition | G-protein-coupled receptor induced protein|G-protein-coupled receptor-induced gene 2 protein|G-protein-coupled receptor-induced protein 2|phosphoprotein regulated by mitogenic pathways|tribbles homolog 1|tribbles-like protein 1 |
Position | 8q24.13 |
Gene type | protein-coding |
Title | Abstract |
| COP1 targets C/EBPalpha for degradation and induces acute myeloid leukemia via Trib1. | 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. |