Studies on the function of Ufd3/Doa1 in the distribution of sterol in yeast

Ufd3/Doa1 (mamallian homologue PLAA) was initially identified as a component involved in the UFD (Ubiquitin Fusion Degradation) pathway. The defects in Ufd3/Doa1 null strain were mainly caused by the loss of ubiquitin levels, because overexpression of ubiquitin can rescue the defects. However, it is still not clear how Ufd3/Doa1maintains the ubiquitin. In addition to the effect on the ubiquitin level, Ufd3/Doa1 was also plays critical roles in sorting of ubiquitinated protein into the vascuolar/lysosome lumen via the MVB pathway. Recently we found that the C‐terminus of PLAA not only interacts with reported p97/Cdc48, but OBP9L, an oxylsterol binding protein like protein. We also confirmed that the interaction between the yeast Ufd3/Doa1 and OSH proteins. Furthermore, we found that yeast Ufd3/Doa1 null strain is sensitive to a polyene antifungal, amphitericin B, which associates with the main component of yeast cell membrane, ergosterol. All these results indicate that Ufd3/Doa1 might play important roles on the sterol system.