TRIB1 (E7N2N) Mouse mAb #58801

TRIBBLES proteins belong to a small family of serine-threonine kinase-like proteins characterized by the presence of a variant protein kinase motif (lacking a canonical ATP binding site), a MEK1 binding site, and a C-terminal COP1 site that binds ubiquitin ligase. The tribbles gene was first identified and characterized in Drosophila genetic screens for genes that regulate cell division, gastrulation, and oogenesis (1-3). Research studies in Drosophila suggested that TRIBBLES functions to coordinate cell division by regulating turnover of the cell cycle protein String/cdc25. In contrast to the Drosophila genome, which contains a single tribbles gene, the genomes of mice and humans encode three known TRIBBLES proteins (TRIB1-3), which exhibit both distinct and overlapping patterns of expression and functions (4). For example, TRIB1 and TRIB2, but not TRIB3, were reported to promote degradation of the basic region-leucine zipper transcription factor C/EBPα, a function that appears to be conserved from flies to humans (5,6). TRIB2 is overexpressed in a subset of human AML patient samples, downregulated in leukemic cells undergoing proliferation arrest (7), and positively regulated by the NOTCH signaling pathway in T cells (8), while retroviral-mediated overexpression of TRIB2 in mice was shown to induce transplantable leukemia (7). These findings collectively suggest that TRIB2 functions as an oncogene in the mammalian hematopoietic system (9).