A human gene, hSGT1, can substitute for GCR2, which encodes a general regulatory factor of glycolytic gene expression in Saccharomyces cerevisiae

Abstract

To determine whether similar regulatory mechanisms control the expression of glycolytic genes in yeast and human cells, we screened a human brain cDNA library for clones which complement the growth defect of the gcr2 mutant of Saccharomyces cerevisiae, and isolated hSGT1 (human suppressor of GCR two). Further work confirmed that the rescue of growth was associated with recovery of glycolytic enzyme activities, and that hSGT1 did not complement the growth defect of a gcr1 mutant. A hybrid protein comprising hSgt1p and the DNA-binding domain of Gal4p (GBD) activated a GAL1-lacZ reporter gene fusion, suggesting that the cloned gene may be a transcriptional activator. Two-hybrid experiments in yeast also indicate that hSgt1p interacts with Gcr1p. Northern analysis showed that hSGT1 is highly expressed in muscle and heart. Although the predicted amino acid sequence of hSgt1p does not display significant similarity to Gcr2p, we speculate that their functions may be analogous.

Amplification of ACK1 promotes gastric tumorigenesis via ECD-dependent p53 ubiquitination degradation

“…The human ECD gene was first identified in a complementation assay conducted to rescue a growth defect in saccharomyces cerevisiae mutants with a GCR2 gene deletion [21]. An ECD deletion in murine embryonic fibroblasts resulted in G1/S arrest through the removal of competitive binding to the Rb protein and subsequent down-regulation of E2F target gene expression [22].…”

“…This finding is consistent with previous reports. In Drosophila, ECD mutants exhibit a general defect in cell survival [32]; in yeast, ECD can rescue the growth defect of the GCR2 mutation [21]. The conditional deletion of ECD in murine embryonic fibroblast cells leads to G1/S arrest [22].…”

Biochemical characterization of human Ecdysoneless reveals a role in transcriptional regulation

“…The authors suggested that hSGT1 may be a functional analog of GCR2. Notably, there is no sequence similarity between hSGT1/hEcd and GCR2 (Sato et al, 1999). …”

“…Given the paucity of knowledge on the structure and function of this protein, we hypothesized that Ecd may have a role in transcriptional regulation based on several lines of evidence: i) in S. cerevisiae , human Ecd is able to bind to GCR1 and act as a coactivator by substituting for GCR2 (Sato et al, 1999), ii) in S. pombe , Ecd was shown to be important in cell survival and loss of its expression suggested a possible role as a transcription regulator (Kainou et al, 2006), iii) human Ecd binds to p53, and increases p53-mediated transcription (Zhang et al, 2006) and iv) hEcd also binds to Rb and regulates Rb/E2F pathway (Kim et al, In press).…”

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression

“…The human ECD homologue was initially identified in a screen of human open reading frames that complemented the S. cerevisiae mutants lacking Gcr2 (glycolysis regulation 2) gene, and it rescued the growth defect caused by reduced glycolytic enzyme activity in Gcr2 mutants. The human gene was initially designated HSGT1 (human suppressor of Gcr2) and was suggested to function as a coactivator of glycolytic gene transcription (4). However, ECD protein bears no structural homology to Gcr2, and a true ECD orthologue is absent in S. cerevisiae, suggesting that ECD likely functions by distinct mechanisms.…”