Tribbles-related protein (TRB) family members are the mammalian orthologs of Drosophila tribbles. Tribbles
was originally identified as a cell cycle regulator during Drosophila development. Tribbles genes are evolutionary
conserved, and three TRB genes (TRB1, TRB2 and TRB3) have been identified in mammals. TRBs are considered
pseudokinases because they lack an ATP binding site or one of the conserved catalytic motifs essential for kinase activity.
Instead, TRBs play important roles in various cellular processes as scaffolds or adaptors to promote the degradation of
target proteins and to regulate several key signaling pathways. Recent research has focused on the role of TRBs in
tumorigenesis and neoplastic progression. In this review, we focus on the physiological roles of TRB family members in
tumorigenesis through the regulation of the ubiquitin-proteasome system and discuss TRBs as biomarkers or potential
therapeutic targets in cancer.
Keywords: Leukemogenesis, oncogene, TRB1, TRB2, TRB3, tumorigenesis, ubiquitin-proteasome system.
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