Inference of Protein Complex Activities from Chemical-Genetic Profile and Its Applications: Predicting Drug-Target Pathways
Figure 6
Target pathway of camptothecin.
(A) The most sensitive protein complex to camptothecin, PC 181, is composed of ULA1 and UBA3, both of which are non-essential genes. Any of components in such complex may be physically associated with RUB1, UBA3, ULA1, UBC12, and RPN4 among gene products deleted in all the sensitive strains to camptothecin. (B) Our proposed model of neddylation-enhanced and ubiquitin-dependent proteasomal degradation of Topoisomerase I-DNA complex stabilized by camptothecin in yeast (details in the text). In this model, we suggest that RUB1-attachment of CUL3 may enhance the degradation of TOP1-cleavable complexes and, therefore, the blocking of RUB1-conjugation pathway contributes to significant increase of the level of camptothecin toxicity in cell growth as shown in PC 181-associated strains.