Fructose-1,6-bisphosphatase, Malate Dehydrogenase, Isocitrate Lyase, Phosphoenolpyruvate Carboxykinase, Glyceraldehyde-3-phosphate Dehydrogenase, and Cyclophilin A are secreted in<i>Saccharomyces cerevisiae</i>grown in low glucose

Giardina, Bennett J.; Chiang, Hung‐Lung

doi:10.4161/cib.27216

Cited by 16 publications

(21 citation statements)

References 41 publications

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“…A notable aspect of GID-mediated processes is the dichotomy between the GID/proteasome-mediated degradation of gluconeogenic enzymes and the "alternative" degradation of these enzymes through an autophagy-related pathway called vacuolar import and degradation (VID) (87,90,93,95,(98)(99)(100). The VID pathway may also involve a GID-mediated polyubiquitylation of gluconeogenic enzymes.…”

mentioning

confidence: 99%

Gid10 as an alternative N-recognin of the Pro/N-degron pathway

Melnykov

Chen

Varshavsky

2019

Proc. Natl. Acad. Sci. U.S.A.

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In eukaryotes, N-degron pathways (formerly “N-end rule pathways”) comprise a set of proteolytic systems whose unifying feature is their ability to recognize proteins containing N-terminal degradation signals called N-degrons, thereby causing degradation of these proteins by the 26S proteasome or autophagy. Gid4, a subunit of the GID ubiquitin ligase in the yeast Saccharomyces cerevisiae, is the recognition component (N-recognin) of the GID-mediated Pro/N-degron pathway. Gid4 targets proteins by recognizing their N-terminal Pro residues or a Pro at position 2, in the presence of distinct adjoining sequence motifs. Under conditions of low or absent glucose, cells make it through gluconeogenesis. When S. cerevisiae grows on a nonfermentable carbon source, its gluconeogenic enzymes Fbp1, Icl1, Mdh2, and Pck1 are expressed and long-lived. Transition to a medium containing glucose inhibits the synthesis of these enzymes and induces their degradation by the Gid4-dependent Pro/N-degron pathway. While studying yeast Gid4, we identified a similar but uncharacterized yeast protein (YGR066C), which we named Gid10. A screen for N-terminal peptide sequences that can bind to Gid10 showed that substrate specificities of Gid10 and Gid4 overlap but are not identical. Gid10 is not expressed under usual (unstressful) growth conditions, but is induced upon starvation or osmotic stresses. Using protein binding analyses and degradation assays with substrates of GID, we show that Gid10 can function as a specific N-recognin of the Pro/N-degron pathway.

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mentioning

confidence: 99%

Gid10 as an alternative N-recognin of the Pro/N-degron pathway

Melnykov

Chen

Varshavsky

2019

Proc. Natl. Acad. Sci. U.S.A.

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“…HPEPDOCK web server 33 is used to perform blind molecular docking for peptides of different lengths (from one amino acid residue up to 20) into the solved structure of Gid4 (PDB ID: 6CCT) using the blind flexible docking approach. HPEPDOCK is a newly released (in the year 2018) web-based software used to blindly dock peptides into proteins using a hierarchical algorithm.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…C, Docking scores of the 20 residues Icl1, Fbp1, and Mdh2 degrons in wild type (red) and (Pro 1 ▶ Ser 1 ) mutated (blue) forms the docking scores (Figure 4), a longer peptide has little influence on the binding affinity. Mdh2 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . Generally, the docking scores and interaction patterns of the three mutated peptides are comparable.…”

Section: N-end Proline Recognitionmentioning

confidence: 99%

“…Isocitrate lyase (Icl1), fructose‐1,6‐bisphosphatase (Fbp1), and malate dehydrogenase (Mdh2) are some of the enzymes that Saccharomyces cerevisiae degrades upon moving to the glucose‐rich environment after a period of a residency in a glucose‐deprived medium. These three enzymes have Proline (Pro 1 ) residue in its N‐terminus …”

Section: Introductionmentioning

confidence: 99%

“…These three enzymes have Proline (Pro 1 ) residue in its Nterminus. [19][20][21] Glucose-induced degradation protein 4 homolog (Gid4), a subunit of Ub ligase GID, is reported to be the recognin for the mentioned gluconeogenic enzymes. 22,23 In 2018, Min and his colleagues introduced the first solved crystal structure of Gid4.…”

Section: Introductionmentioning

confidence: 99%

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Recognition of gluconeogenic enzymes; Icl1, Fbp1, and Mdh2 by Gid4 ligase: A molecular docking study

Elfiky

Ismail

Elshemey

2019

J of Molecular Recognition

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The pro/N‐degron pathway is an evolved protein degradation pathway through the ubiquitin‐proteasome system. It is a vital pathway to attain protein homeostasis inside the liver cells with varying glucose levels. N‐terminal proline exists in more than 300 proteins in Saccharomyces cerevisiae, but only three of them are the gluconeogenic enzymes; isocitrate lyase (Icl1), fructose‐1,6‐bisphosphatase (Fbp1), and malate dehydrogenase (Mdh2). The present in silico study aims to structurally illustrate the binding of Icl1 enzyme to Gid4 ligase concerning its peers; Fbp1 and Mdh2. Based on the molecular docking scores and interactions, one can attribute the binding stability of Gid4 with degrons, to peptides of length six up to eight from the N‐terminal. Moreover, the percent change in the docking score provides a rationale for the unique Gid4‐Icl11‐4 interaction. The present study provides insights on the binding attitude of Gid4 ligase to degrons of different lengths, so one will consider in designing peptidomimetics to target Gid4 ligase.

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Fructose‐1,6‐bisphosphatase degradation in the methylotrophic yeast Komagataella phaffii occurs in autophagy pathway

Dmytruk

Bulbotka

Zazulya

et al. 2020

Cell Biology International

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Many enzymes of methanol metabolism of methylotrophic yeasts are located in peroxisomes whereas some of them have the cytosolic localization. After shift of methanol‐grown cells of methylotrophic yeasts to glucose medium, a decrease in the activity of cytosolic (formaldehyde dehydrogenase, formate dehydrogenase, and fructose‐1,6‐bisphosphatase [FBP]) along with peroxisomal enzymes of methanol metabolism is observed. Mechanisms of inactivation of cytosolic enzymes remain unknown. To study the mechanism of FBP inactivation, the changes in its specific activity of the wild type strain GS200, the strain with the deletion of the GSS1 hexose sensor gene and strain defected in autophagy pathway SMD1163 of Komagataella phaffii with or without the addition of the MG132 (proteasome degradation inhibitor) were investigated after shift of methanol‐grown cells in glucose medium. Western blot analysis showed that inactivation of FBP in GS200 occurred due to protein degradation whereas inactivation in the strains SMD1163 and gss1Δ was negligible in such conditions. The effect of the proteasome inhibitor MG132 on FBP inactivation was insignificant. To confirm FBP degradation pathway, the recombinant strains with GFP‐labeled Fbp1 of K. phaffii and red fluorescent protein‐labeled peroxisomes were constructed on the background of GS200 and SMD1163. The fluorescent microscopy analysis of the constructed strains was performed using the vacuolar membrane dye FM4‐64. Microscopic data confirmed that Fbp1 degrades by autophagy pathway in K. phaffii. K. phaffii transformants, which express heterologous β‐galactosidase under FLD promoter, have been constructed.

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Fructose-1,6-bisphosphatase, Malate Dehydrogenase, Isocitrate Lyase, Phosphoenolpyruvate Carboxykinase, Glyceraldehyde-3-phosphate Dehydrogenase, and Cyclophilin A are secreted inSaccharomyces cerevisiaegrown in low glucose

Cited by 16 publications

References 41 publications

Gid10 as an alternative N-recognin of the Pro/N-degron pathway

Gid10 as an alternative N-recognin of the Pro/N-degron pathway

Recognition of gluconeogenic enzymes; Icl1, Fbp1, and Mdh2 by Gid4 ligase: A molecular docking study

Fructose‐1,6‐bisphosphatase degradation in the methylotrophic yeast Komagataella phaffii occurs in autophagy pathway

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