A systematic genetic screen for genes involved in sensing inorganic phosphate availability in Saccharomyces cerevisiae.

TitleA systematic genetic screen for genes involved in sensing inorganic phosphate availability in Saccharomyces cerevisiae.
Publication TypeJournal Article
Year of Publication2017
AuthorsChoi, J, Rajagopal, A, Xu, Y-F, Rabinowitz, JD, O'Shea, EK
JournalPLoS One
Volume12
Issue5
Paginatione0176085
Date Published2017
ISSN1932-6203
Abstract

Saccharomyces cerevisiae responds to changes in extracellular inorganic phosphate (Pi) availability by regulating the activity of the phosphate-responsive (PHO) signaling pathway, enabling cells to maintain intracellular levels of the essential nutrient Pi. Pi-limitation induces upregulation of inositol heptakisphosphate (IP7) synthesized by the inositol hexakisphosphate kinase Vip1, triggering inhibition of the Pho80/Pho85 cyclin-cyclin dependent kinase (CDK) complex by the CDK inhibitor Pho81, which upregulates the PHO regulon through the CDK target and transcription factor Pho4. To identify genes that are involved in signaling upstream of the Pho80/Pho85/Pho81 complex and how they interact with each other to regulate the PHO pathway, we performed genome-wide screens with the synthetic genetic array method. We identified more than 300 mutants with defects in signaling upstream of the Pho80/Pho85/Pho81 complex, including AAH1, which encodes an adenine deaminase that negatively regulates the PHO pathway in a Vip1-dependent manner. Furthermore, we showed that even in the absence of VIP1, the PHO pathway can be activated under prolonged periods of Pi starvation, suggesting complexity in the mechanisms by which the PHO pathway is regulated.

DOI10.1371/journal.pone.0176085
Alternate JournalPLoS ONE
PubMed ID28520786
PubMed Central IDPMC5435139