TRIB3 (E7G5P) Rabbit Monoclonal Antibody #43043

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).

Enhanced TRIB3 expression has been associated with cancer development, cancer radiotherapy resistance, as well as liver fibrosis (10,11). The protein mainly functions by interacting with a wide variety of key regulators, such as EGFR, Akt, β-catenin, TAZ, and SQSTM1, to promote their functions in these disease development processes (11-14).