Disease relevance of SLG1

• Deletion of the SLG1 gene in parental strains caused hypersensitivity to bleomycin, and this correlated with an accumulation of damaged DNA [1].

High impact information on SLG1

• Finally, in chlorpromazine-treated cells, this response does not require Wsc1p or the protein kinase Pkc1p, both of which are upstream of the transcriptional repression of ribosomal components [2].
• We find that another dose-dependent suppressor of swi4 mutants, the novel gene HCS77, encodes a putative integral membrane protein [3].
• Our data suggest that in yeast, O mannosylation increases the activity of Wsc1p, Wsc2p, and Mid2p by enhancing their stability [4].
• In a related line of investigation, we identified the PMT2 gene in a genetic screen for mutations that confer an additive cell lysis defect with a wsc1 null allele [5].
• At least with regard to Wsc1, this interaction is mediated by the Rom2 N-terminal domain [5].

Biological context of SLG1

• Consistent with this idea, it was found that perturbations in Rho3-mediated polarized exocytosis specifically impair the abundance and processing of Wsc1 and Mid2 proteins [6].
• A screen for upstream components of the yeast protein kinase C signal transduction pathway identifies the product of the SLG1 gene [7].
• Thus, in the strain used for mutagenesis, disruption of SLG1 causes the cells to become non-viable in the absence of osmotic stabilization at both 30 degrees C and 37 degrees C. In a different genetic background this phenotype was not observed [7].
• (1) Deletion of LRG1 suppresses the growth phenotypes associated with mutations in SLG1 (which codes for a putative sensor of cell wall damage) [8].
• We conclude that Hcs77 is dedicated to signaling cell wall stress during vegetative growth and that Mid2 participates in this signaling, but its primary role is in signaling wall stress during pheromone-induced morphogenesis [9].

Anatomical context of SLG1

• Wsc1 and Mid2 are highly O-glycosylated cell surface proteins that reside in the plasma membrane of Saccharomyces cerevisiae [5].
• Co-inactivation of RGD1 and WSC1, which is a cell wall sensor-encoding gene, is lethal [6].
• Mutations in genes necessary for endosome to Golgi traffic caused redistribution of Wsc1p from the cell surface to internal compartments, indicative of recycling [10].
• The cell wall sensor Wsc1p is involved in reorganization of actin cytoskeleton in response to hypo-osmotic shock in Saccharomyces cerevisiae [11].

Associations of SLG1 with chemical compounds

• As for mutants altered in PKC pathway, the accumulation of small-budded dead cells in slg1, rgd1 and mid2 after heat shock was prevented by 1 M sorbitol [12].
• Haploid slg1 deletion strains are sensitive to caffeine, as expected for mutants in the Pkc pathway, as well as a variety of other drugs [7].
• A plasmid that expresses the native SLG1 gene or that increases PKC1 gene dosage restored bleomycin resistance to the slg1Delta mutant [1].
• Extraction experiments show that Wsc1p is an integral membrane protein present in two forms: one solubilized by detergent, the other Triton X-100 insoluble [13].
• Analysis of the properties and function of the mutant proteins shows that the predicted extracellular serine/threonine-rich domain is required for Wsc1p functionality, as well as its glycosylation [13].

Regulatory relationships of SLG1

• Mutation of NPFDD in Wsc1p or expression of Sla1p lacking SHD1 blocked Wsc1p internalization [10].

Other interactions of SLG1

• It was proposed that simultaneous inactivation of RGD1 and WSC1 constitutively activates the PKC-mitogen-activated protein kinase (MAP kinase) pathway [6].
• Initially, SLG1 and PKC1 were obtained as high-copy suppressors of dsk2Delta rad23Delta and a mutation in MPK1 was synthetically lethal with kar1-Delta17 [14].
• The cell wall and stress response component (Wsc) protein family in the yeast Saccharomyces cerevisiae is encoded by at least three genes, WSC1, WSC2, and WSC3 [15].

Analytical, diagnostic and therapeutic context of SLG1

• Wsc1p was found to fractionate with the membrane pellet after high-speed centrifugation [13].
• Two-dimensional gel electrophoresis revealed that exposure to bleomycin triggered the expression of certain proteins, presumably to maintain cell wall function, in a Slg1-dependent manner [1].

References