Inference of Protein Complex Activities from Chemical-Genetic Profile and Its Applications: Predicting Drug-Target Pathways
Figure 5
(A) The most sensitive protein complex to rapamycin, PC 321, is composed of ERG1 and SEC2, both of which are essential genes. Any of components in such complex may be physically or genetically associated with ELP3, TEF4, and TOR1 among gene products deleted in all the sensitive strains to rapamycin. According to model assumption, it can be interpreted as follows: Strains of complex-associated gene deletions have deleterious biological interactions with that complex. It may lead to decrease in the growth fitness of those strains in rapamycin. (B) Target of Rapamycin (TOR) pathway primarily regulated by Target of Rapamycin Complex 1(TORC1) with/without rapamycin. When the rapamycin is treated in a yeast cell, it binds FKBP12, forming toxic complex, which inhibits specifically TOR1, an essential component of TORC1. It gives rise to abnormal TORC1 signaling cascades related to broad biological functions, transcription, translation, mRNA stability and permeability.