High impact information on CAT8

• Glucose derepression of gluconeogenesis depends on the active Cat1 (Snf1) protein kinase and the Cat8 zinc cluster activator [1].
• Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets [2].
• The Snf1-Cat8 connection is evolutionarily conserved: mutation of corresponding serine 562 of ScCat8p gave similar results in S. cerevisiae [3].
• This finding suggests an upstream activating function of this promoter region, which is Mig1p independent, as delta mig1 mutants are still able to derepress the CAT8 promoter [4].
• No other putative binding sites such as a Hap2/3/4/5p site and an Abf1p consensus site were functional with respect to glucose-regulated CAT8 expression [4].

Biological context of CAT8

• Thus, biosynthetic control of CAT8 as well as transcriptional activation by Cat8p requires a functional Cat1p protein kinase [5].
• A constitutively expressed GAL4-CAT8 fusion gene revealed a carbon source-dependent transcriptional activation of a UAS(GAL)-containing reporter gene [5].
• This finding indicates that region-A1-mediated gene expression is regulated by a pathway independent of CAT8, which is necessary for derepression of CSRE-mediated gene expression in S. cerevisiae [6].
• These results confirm our current model that glucose derepression of gluconeogenic genes needs Cat8p phosphorylation and additionally show that a still unknown transcriptional activator is also involved [4].
• This activation capacity was still carbon source regulated and depended on the Cat1p (Snf1p) protein kinase, which indicated that Cat8p needs posttranslational modification to reveal its gene-activating function [4].

Associations of CAT8 with chemical compounds

• Deletion of CAT8 caused a defect in glucose derepression which affected all key gluconeogenic enzymes [7].
• ADR1 and CAT8 encode carbon source-responsive transcriptional regulators that cooperatively control expression of genes involved in ethanol utilization [8].
• It appears that the biochemical functions of the proteins encoded by Cat8p-dependent genes are essentially related to the first steps of ethanol utilization, the glyoxylate cycle, and gluconeogenesis [9].
• Three target genes for the transcriptional activator Cat8p of Kluyveromyces lactis: acetyl coenzyme A synthetase genes KlACS1 and KlACS2 and lactate permease gene KlJEN1 [10].
• The succinate/fumarate transporter Acr1p of Saccharomyces cerevisiae is part of the gluconeogenic pathway and its expression is regulated by Cat8p [11].

Physical interactions of CAT8

• In conclusion, these results show a derepression of ADH2 by synergistically acting regulators Adr1 (interacting with UAS1) and Cat8, binding to UAS2 (=CSRE(ADH2)) [12].

Regulatory relationships of CAT8

• Expression of CAT8 is carbon source regulated and requires a functional Cat1p (Snf1p) protein kinase [5].

Other interactions of CAT8

• A CAT8-lacZ promoter fusion revealed that the CAT8 gene itself is repressed by Cat4p (Mig1p) [7].
• The CAT8 gene encodes a zinc cluster protein related to Saccharomyces cerevisiae Gal4p [7].
• Derepression of CAT8 also requires a functional HAP2 gene, suggesting a regulatory connection between respiratory and gluconeogenic genes [5].
• We have isolated a regulatory gene, DIL1 (derepression of isocitrate lyase, = CAT8), which is specifically required for derepression of CSRE-dependent genes [5].
• Only a small number of ADR1-dependent genes are also CAT8-dependent [8].

Analytical, diagnostic and therapeutic context of CAT8

• Gel retardation assays provide evidence for a different binding affinity of Cat8 and Sip4 to at least some CSRE sequence variants [13].

References