The previously identified BUL1 gene was found to encode a protein bound to Rsp5-ubiquitin ligase in budding yeast. We have identified the BUL2 gene as a functional homologue of BUL1. The bul1 bul2 double disruptant was sensitive to various stresses, such as high temperature, salts, and a non-fermentable carbon source. Each Bul protein has a putative PY-motif that has been predicted to interact with one of three WW-domains of Rsp5. A mutant Bul1 containing an altered PY-motif was defective in ability to bind to Rsp5 in the two-hybrid system and hardly co-immunoprecipitated with Rsp5. Furthermore, the mutant was not able to overcome all growth defects of the double disruptant. Thus, Bul proteins are essential for growth in various stress conditions, and their functions are mediated through the PY-motif, probably by binding to Rsp5.