Disease relevance of STD1

• Cells with null alleles in both STD1 and its homologue, MTH1, manifest numerous phenotypes observed in calcineurin mutants, including sodium, lithium, manganese, and hydroxyl ion sensitivity, as well as alpha factor toxicity [1].

High impact information on STD1

• These results support a model of glucose signaling in which glucose binding to the glucose sensors causes them to activate Yck1 in the cell membrane, which then phosphorylates Mth1 and Std1 bound to the cytoplasmic face of the glucose sensors, triggering their degradation and leading to the derepression of HXT gene expression [2].
• Std1 and Mth1 proteins interact with the glucose sensors to control glucose-regulated gene expression in Saccharomyces cerevisiae [3].
• A two-hybrid screen for Std1-interacting proteins identified the hydrophilic C-terminal domains of the glucose sensors, Snf3 and Rgt2 [3].
• The Std1 protein modulates the expression of glucose-regulated genes, but its exact molecular role in this process is unclear [3].
• Finally, studies with green fluorescent protein fusions indicate that Std1 is localized to the cell periphery and the cell nucleus, supporting the idea that it may transduce signals from the plasma membrane to the nucleus [3].

Biological context of STD1

• Gene expression studies indicate that the regulation of HAL1 and PMR2 expression is affected by STD1 gene dosage [1].
• Furthermore, increased gene dosage of STD1 suppresses the ion stress phenotypes in calcineurin mutants and confers halotolerance in wild-type cells [1].
• The activation of SUC2 expression by increased copy number of STD1 occurs at the level of mRNA accumulation and it requires the same TATA element and uses the same transcription start site as does activation of SUC2 by glucose limitation [4].
• The STD1 gene contains a single continuous open reading frame with the potential to encode a 50.2-kDa protein [5].
• These findings suggest that Std1p stimulates the Snf1 kinase by an interaction with the catalytic domain that antagonizes autoinhibition and promotes an active conformation of the kinase [6].

Associations of STD1 with chemical compounds

• The consequence of relieving feedback regulation of STD1 expression is that reestablishment of repression of HXT1 expression upon removal of glucose is delayed [7].

Physical interactions of STD1

• STD1 (MSN3) interacts directly with the TATA-binding protein and modulates transcription of the SUC2 gene of Saccharomyces cerevisiae [4].
• We report here a direct physical interaction between STD1 and the TATA-binding protein (TBP), observed in vivo by the two-hybrid system and in vitro by binding studies [4].
• Finally, MSN3 physically interacts with the SNF1 protein kinase, as assayed by a two-hybrid system and by in vitro binding studies [8].
• We report that Rgt1 interacts with Std1 and Mth1 in a yeast two-hybrid assay and co-immunoprecipitates with both proteins in vivo only when glucose is absent [9].

Regulatory relationships of STD1

• Std1 mutants that lost the ability to induce SUC2, were also unable to suppress the growth defect caused by the expression of the dominant negative TBPDelta57 protein, suggesting that these two genetic screens may be detecting the same biological activity [10].

Other interactions of STD1

• In media lacking glucose or with low levels of glucose, the hexose transporter genes are subject to repression by a mechanism that requires the Std1 and Mth1 proteins [3].
• Amino acid residues in Std1 protein required for induction of SUC2 transcription are also required for suppression of TBPDelta57 growth defect in Saccharomyces cerevisiae [10].
• Disappearance of Std1 in response to glucose is accelerated when glucose induction of STD1 expression due to feedback regulation by Rgt1 is prevented [7].
• Overexpression of Std1p elevated Snf1 kinase activity in both in vitro and in vivo assays [6].
• Here we report the sequence and initial characterization of one suppressor, designated STD1 for suppressor of TBP deletion [5].

Analytical, diagnostic and therapeutic context of STD1

• Two-hybrid assays showed that Std1p interacts with the catalytic domain of Snf1p, and analysis of mutant kinases suggested that this interaction is incompatible with the autoinhibitory interaction of the regulatory and catalytic domains [6].

References