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Role for the molecular chaperones Zuo1 and Ssz1 in quorum sensing via activation of the transcription factor Pdr1

Zuo1 functions as a J-protein cochaperone of its partner Hsp70. In addition, the C terminus of Zuo1 and the N terminus of Ssz1, with which Zuo1 forms a heterodimer, can independently activate the Saccharomyces cerevisiae transcription factor pleiotropic drug resistance 1 (Pdr1). Here we report that activation of Pdr1 by Zuo1 or Ssz1 causes premature growth arrest of cells during the diauxic shift, as they adapt to the changing environmental conditions. Conversely, cells lacking Zuo1 or Ssz1 overgrow, arresting at a higher cell density, an effect overcome by activation of Pdr1. Cells lacking the genes encoding plasma membrane transporters Pdr5 and Snq2, two targets of Pdr1, also overgrow at the diauxic shift. Adding conditioned medium harvested from cultures of wild-type cells attenuated the overgrowth of both zuo1Δssz1Δ and pdr5Δsnq2Δ cells, suggesting the extracellular presence of molecules that signal growth arrest. In addition, our yeast two-hybrid analysis revealed an interaction between Pdr1 and both Zuo1 and Ssz1. Together, our results support a model in which (i) membrane transporters, encoded by Pdr1 target genes act to promote cell–cell communication by exporting quorum sensing molecules, in addition to playing a role in pleiotropic drug resistance; and (ii) molecular chaperones function at promoters to regulate this intercellular communication through their activation of the transcription factor Pdr1.