Ubiquitin itself can be ubiquitinated on any of its seven internal lysines and one internal methionine. The addition of ubiquitin onto proteins requires the orchestrated action of E1 (ubiquitin activating), E2 (ubiquitin conjugating) and E3 (ubiquitin ligating) enzymes in a well-defined ATP-dependent cascade. The UPS specifies proteins for degradation by covalent conjugation of a 76 amino acid ubiquitin peptide which directs them to 26S proteasomes, for cleavage into short polypeptides and composite amino acids for reuse in the cell. In eukaryotic cells, the ubiquitin–proteasome system (UPS) is a highly regulated and selective pathway controlling this process. Here, we review and explore the FBXL family members in detail highlighting their structural and functional similarities and differences and how they engage their substrates through their LRRs to adopt unique interactomes.Ĭore cellular processes, like cell division and cell death induction, use protein degradation to bring about swift transitions and definitive outcomes for the cell. But how the 22 FBPs of the FBXL family achieve their individual specificities, despite having highly similar structural domains to recruit their substrates, is not clear. The FBXL subfamily is defined by the presence of multiple leucine-rich repeat (LRR) protein-binding domains. To date, around 70 FBPs have been identified in humans and can be subdivided into distinct families, based on the protein-recruiting domains they possess. F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin ligases that determine which proteins are ubiquitinated. The ubiquitin–proteasome system (UPS) is responsible for the rapid targeting of proteins for degradation at 26S proteasomes and requires the orchestrated action of E1, E2 and E3 enzymes in a well-defined cascade.
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