Authors

Discussion

Recent evidence links cullin-RING complexes to the regulation of the surface of Trypanosoma brucei as well as other functions. This is the interface between the host and the parasite and  determinant for the uptake of trypanocidal drugs. In mammalian systems, cullins are key regulators of the cell cycle, control ubiquitination pathways involved in receptor internalisation and have been suggested as drug targets.Despite the broad scope of the ubiquitination pathways in the Kinetoplastida and its potential to impact the entirety of trypanosome biology our current understanding of the cullin RING ligases is extremely limited. We have identified and assembled a phylogenetic reconstruction of the cullin family in the Kinetoplastida as well as a number of adaptor proteins and E3 ligases. Using cryo-milling and immunoisolation we have identified components of the TbCUL1 complex. Proteomic analysis revealed multiple protein abundance changes upon TbCUL1 silencing, including F-box and WD-repeats proteins, which homologues have been described as substrates for  cullin RING ligases. These data provide a first systematic assessment of cullin composition and function.