SUMMARY PARAGRAPH for GAC1
Gac1p is a regulator of the Glc7p type-1 protein phosphatase (PP1), and functions as a molecular scaffold to tether Glc7p to the Gsy2p glycogen synthase (3). Gsy2p activity is inhibited by phosphorylation, and the Glc7p-Gac1p holoenzyme is required to dephosphorylate and activate Gsy2p (4, 2). Gac1p also binds the Hsf1p heat shock transcription factor, and Gac1p and Glc7p are both required for the induction of some HSF-regulated genes under heat shock (7).
Gac1p contains a conserved GVNK motif of approximately 25 residues that is also found in mammalian type 1 phosphatase targeting subunits (RGI proteins) (8, 9). The GAC1 promoter contains an STRE sequence, and expression of GAC1 is repressed by Ssa1p, Ssa2p, and cAMP-dependent protein kinase (PKA) (10, 11). GAC1 expression is induced during the diauxic transition, beginning when approximately 50% of the available glucose is consumed, and reaches a maximum at the diauxic shift (12). Gac1p abundance increases during growth with the same kinetics as glycogen accumulation (13). Gac1p is phosphorylated in vivo, is hyperphosphorylated in a glc7-1 mutant, and may be a substrate of Cdc28p (13, 5).
gac1 null mutants accumulate decreased levels of glycogen, increased levels of inactive, hyperphosphorylated Gsy2p (3, 13), and also display decreased transcription of some heat shock factor responsive genes during heat shock (7). Overexpression of GAC1 results in increased Gsy2p activity and glycogen accumulation, partial glucose derepression, and increased salt sensitivity (2, 13).
Last updated: 2005-10-07