title: Synthetic lethal interactions in yeast reveal functional roles of J protein co-chaperones.
abstract: J proteins are a diverse family of co-chaperones that cooperate with heat shock protein 70 (Hsp70) to coordinate protein quality control, especially in response to cellular stress. Current models suggest that individual J proteins might play roles in recruiting Hsp70s to specific functions, such as maintaining cell wall integrity or promoting ribosome biogenesis. However, relatively few stresses have been used to test this model and, as a result, only a few specific activities have been identified. To expand our understanding of the J protein network, we used a synthetic lethal approach in which 11 Saccharomyces cerevisiae deletion strains were treated with 12 well-characterized chemical inhibitors. The results defined new roles for specific J proteins in major signaling pathways. For example, an important role for Swa2 in cell wall integrity was identified and activities of the under-explored Jjj1, Apj1, Jjj3 and Caj1 proteins were suggested. More generally, these findings support a model in which some J proteins, such as Ydj1 and Zuo1, play "generalist" roles, while others, such as Apj1 and Jjj2, are "specialists", having roles in relatively few pathways. Together, these results provide new insight into the network of J proteins.
authors.affiliation: Departments of Pathology and Biological Chemistry and the Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Gillies
authors.forename: Rebecca
authors.initials: R
authors.lastname: Taylor
authors.forename: Jason E
authors.initials: JE
authors.lastname: Gestwicki
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C574594:APJ1 protein, S cerevisiae; C088621:CAJ1 protein, S cerevisiae; D002148:Calmodulin-Binding Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C517792:Jjj1 protein, S cerevisiae; D018832:Molecular Chaperones; D010750:Phosphoproteins; C419865:SWA2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C070319:YDJ1 protein, S cerevisiae