TRIB3 Human
Description
Product Specs
Product Science Overview
Tribbles Pseudokinase 3 (TRIB3) is a member of the Tribbles family of pseudokinases, which also includes TRIB1 and TRIB2. Pseudokinases are proteins that resemble kinases but lack catalytic activity due to the absence of crucial amino acids required for ATP binding and transfer. Despite their lack of enzymatic activity, pseudokinases play significant roles in cellular signaling by acting as scaffolds or adaptors for other proteins.
The first Tribbles protein was identified in the fruit fly, Drosophila melanogaster, where it was found to be critical for the coordination of morphogenesis. The human homologs of Tribbles proteins were subsequently identified and named TRIB1, TRIB2, and TRIB3. Initially, the human TRIB3 gene was named “Tribbles homolog 3 (Drosophila)” to reflect its evolutionary relationship with the Drosophila protein. However, in 2016, the HUGO Gene Nomenclature Committee renamed it to “Tribbles pseudokinase 3” to emphasize its function as a pseudokinase .
TRIB3 has a structure similar to classic serine/threonine kinases but lacks the conserved amino acids necessary for catalytic activity. This results in very weak ATP affinity, classifying TRIB3 as a pseudokinase. Despite its lack of kinase activity, TRIB3 interferes with a broad range of cellular processes through protein-protein interactions. It acts as an adaptor or scaffold protein for many other proteins, including kinase-dependent proteins, transcription factors, ubiquitin ligases, and components of the spliceosome machinery .
TRIB3 is involved in various cellular processes, including the regulation of apoptosis, cell survival, and stress responses. It is induced by the transcription factor NF-kappaB and acts as a negative regulator of NF-kappaB signaling. TRIB3 can sensitize cells to TNF- and TRAIL-induced apoptosis and negatively regulate the cell survival serine-threonine kinase AKT1 .
Accumulating evidence supports a key function for Tribbles proteins in oncogenesis, both in leukemia and solid tumors. TRIB3’s role in cancer is complex and context-dependent, as it can function as both an oncogene and a tumor suppressor. TRIB3 interacts with and regulates the activity of many key signaling components, influencing cancer development, progression, and metastasis. Dysregulation of TRIB3 can be associated with either good or bad prognosis, depending on the context .
