title: Genome-wide expression analysis reveals TORC1-dependent and -independent functions of Sch9.
abstract: The protein kinase Sch9 is proposed to be a downstream effector of TORC1 that is required for activation of ribosome biogenesis and repression of entry into G(0). However, Sch9 apparently functions antagonistically to TORC1, when considering the induction of several stress defence genes that are normally repressed by TORC1. To further investigate the relationship between Sch9 and TORC1, we compared the rapamycin-induced transcriptional responses in an sch9Delta mutant and the isogenic wild type. The data indicate that Sch9 is necessary for proper integration of the rapamycin-induced stress signal, i.e. in sch9Delta cells, typical effects of rapamycin-like repression of ribosomal protein genes and induction of stress response genes are diminished or abolished. Moreover, they reveal for the first time a direct link between Sch9 and nitrogen metabolism. A sch9Delta mutant has an increased basal activation of targets of the general amino acid control pathway and of the nitrogen discrimination pathway, including the ammonium permease MEP2 and the amino acid permease GAP1. The mutant also shows enhanced expression of the transcription factor Gcn4 required for amino acid biosynthesis. Our data favour a model in which (1) the role of Sch9 in the general stress response switches depending on TORC1 activity and (2) Sch9 and TORC1 have independent and additive effects on genes induced upon nitrogen and amino acid starvation.
authors.affiliation: Laboratory of Functional Biology, Katholieke Universiteit Leuven, Heverlee, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Smets
authors.forename: Pepijn
authors.initials: P
authors.lastname: De Snijder
authors.forename: Kristof
authors.initials: K
authors.lastname: Engelen
authors.forename: Eva
authors.initials: E
authors.lastname: Joossens
authors.forename: Ruben
authors.initials: R
authors.lastname: Ghillebert
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx