Disease relevance of SCH9

• This is the first biochemical demonstration of Sch9 activators, and the results further support roles for long chain bases in heat stress resistance in addition to implying roles in chronological aging and cell size determination, since Sch9 functions in these processes [1].

High impact information on SCH9

• Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension [2].
• These findings suggest that nutrient signals set the critical cell-size threshold via Sfp1 and Sch9-mediated control of ribosome biosynthetic rates [3].
• Here, we show that two potent negative regulators of Start, Sfp1 and Sch9, are activators of the ribosomal protein (RP) and ribosome biogenesis (Ribi) regulons, the transcriptional programs that dictate ribosome synthesis rate in accord with environmental and intracellular conditions [3].
• Cells lacking SCH9 grow slowly and have a prolonged G1 phase of the cell cycle [4].
• SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits [4].

Biological context of SCH9

• Sch9p may affect signal transduction pathways which regulate proteins that are specifically required for HOT1-stimulated exchange [5].
• To investigate the role of the AUGs within the uORF, we engineered chimaeric plasmid vectors in which SCH9 sequences including the promoter, the mRNA leader and the first 514 nucleotides of the major ORF were fused in-frame with beta-galactosidase-coding sequences [6].
• The SCH9 protein kinase mRNA contains a long 5' leader with a small open reading frame [6].
• Sfp1 and Sch9 are required for carbon-source modulation of cell size and are regulated at the level of nuclear localization and abundance, respectively [3].
• We also demonstrate for the first time that Pkh1 phosphorylates the Sch9 protein kinase in vitro and that such phosphorylation is stimulated by PHS [1].

Anatomical context of SCH9

• Here we show that mutations in CYR1 and SCH9 also extend the replicative life span of individual yeast mother cells [7].
• Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G(0), a key developmental process in eukaryotic cells [8].

Associations of SCH9 with chemical compounds

• The deletion of SCH9, which encodes for a serine threonine kinase, triples the mean life span and increases resistance to oxidative and thermal stress [9].
• Deletion of the SCH9 gene encoding a protein kinase involved in nutrient-induced signal transduction restored glucose-induced trehalase activation in Pph22-overexpressing cells [10].
• The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9 [11].
• The sphingoid long chain base phytosphingosine activates AGC-type protein kinases in Saccharomyces cerevisiae including Ypk1, Ypk2, and Sch9 [1].
• The data presented are consistent with a cyclic AMP (cAMP)-gating phenomenon recognized in higher eukaryotes consisting of a main gatekeeper, the protein kinase PKA, switching on or off the activities and signals transmitted through primary pathways such as, in case of yeast, the Sch9-controlled signalling route [12].

Enzymatic interactions of SCH9

• Sch9 phosphorylates Sko1 in vitro [13].

Regulatory relationships of SCH9

• These results are consistent with a model in which the GPR1/GPA2 pathway activates the Sch9p kinase to generate a response that acts in parallel with that generated by the Ras/cAMP pathway, resulting in the integration of nutrient signals [14].
• Both activation of PKA or overexpression of SOK1 or SCH9-two genes isolated as multicopy suppressors of a PKA null mutant-suppress the mbr1 growth defect [15].
• The Sch9 protein kinase regulates Hsp90 chaperone complex signal transduction activity in vivo [16].
• Unlike PKA, which negatively regulates stress-responsive element (STRE)- and post-diauxic shift (PDS)-driven gene expression, Sch9 appears to exert additional positive control on the Rim15-effector Gis1 to regulate PDS-driven gene expression [12].
• The Yak1 protein kinase of Saccharomyces cerevisiae moderates thermotolerance and inhibits growth by an Sch9 protein kinase-independent mechanism [17].

Other interactions of SCH9

• SCH9 was found to be required for ADH2 expression in contrast to the inhibitory role played by cAPK [18].
• Deletion of SCH9 decreases HOT1 and rDNA recombination but not other mitotic exchange [5].
• TPK1, which encodes a catalytic subunit of PKA, is a multicopy suppressor of the recombination and growth defects of sch9 mutants, suggesting that increased PKA activity compensates for SCH9 loss [5].
• RAS2( val19), which codes for a hyperactive RAS protein and increases PKA activity, suppresses both phenotypic defects of sch9 mutants [5].
• In this report, we demonstrate a novel synthetic genetic interaction between SSE1 and SCH9 [19].

References