TRIB2 and the ubiquitin proteasome system in cancer.

Tribbles family of pseudokinase proteins are known to mediate the degradation of target proteins in Drosophila and mammalian systems. The main protein proteolysis pathway in eukaryotic cells is the ubiquitin proteasome system (UPS). The tribbles homolog 2 (TRIB2) mammalian family member has been well characterized for its role in murine and human leukaemia, lung and liver cancer. One of the most characterized substrates for TRIB2-mediated degradation is the myeloid transcription factor CCAAT enhancer binding protein α (C/EBPα). However, across a number of cancers, the molecular interactions that take place between TRIB2 and factors involved in the UPS are varied and have differential downstream effects. This review summarizes our current knowledge of these interactions and how this information is important for our understanding of TRIB2 in cancer.