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Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus

GAPDH and apoptosis in animal cells. Interactions and processes that have been observed in different studies and cell types are here summarized in a single hypothetical animal cell. Different apoptotic stimuli may induce NO biosynthesis and the figure shows how apoptosis in animal cells may be triggered by the initial nitrosylation of GAPDH, and counteracted by several processes. For a detailed explanation, see text (Animal GAPDH: redox-dependent non-glycolytic (moonlighting) functions). GOSPEL, GAPDH’s competitor Siah1 protein enhances life; N-CoR, nuclear co-repressor; Siah1, seven in absentia homologue 1.
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Figure 8: GAPDH and apoptosis in animal cells. Interactions and processes that have been observed in different studies and cell types are here summarized in a single hypothetical animal cell. Different apoptotic stimuli may induce NO biosynthesis and the figure shows how apoptosis in animal cells may be triggered by the initial nitrosylation of GAPDH, and counteracted by several processes. For a detailed explanation, see text (Animal GAPDH: redox-dependent non-glycolytic (moonlighting) functions). GOSPEL, GAPDH’s competitor Siah1 protein enhances life; N-CoR, nuclear co-repressor; Siah1, seven in absentia homologue 1.

Mentions: Animal GAPDH is involved in the signaling cascade that governs NO-dependent apoptosis. After apoptotic stimuli, GAPDH is found in the nucleus in a number of cell systems, including neurons (Nakamura and Lipton, 2013). A fundamental prerequisite for GAPDH relocalization from the cytoplasm to the nucleus appears to be the S-nitrosylation of its catalytic cysteine. Diverse apoptotic stimuli induce NO biosynthesis in animal cells and S-nitrosylated GAPDH (SNO-GAPDH) acquires the ability to bind Siah1 (seven in absentia homologue 1), an E3-ubiquitin ligase with a nuclear localization signal (Figure 8). The SNO-GAPDH/Siah1 interaction is mediated by the C-terminal catalytic domain of GAPDH and has the effect of increasing the stability of Siah1. The complex SNO-GAPDH/Siah1 translocates to the nucleus and mediates cell death (Figure 8; Hara et al., 2005). Different mechanisms are involved in SNO-GAPDH/Siah1-mediated apoptosis (Figure 8). Diverse nuclear proteins are ubiquitinated by Siah1, including the nuclear co-repressor N-CoR (Hara et al., 2005), and SNO-GAPDH/Siah1 can also bind to acetyltransferase p300/CBP and in turn be acetylated on Lys-160. Interestingly, this interaction (in which Lys-160 of GAPDH plays an essential role) stimulates the autoacetylation of p300 and activates the acetylation of downstream targets like tumor suppressor p53 and others that, upon activation, induce cell death (Sen et al., 2008).


Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties.

Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P - Front Plant Sci (2013)

GAPDH and apoptosis in animal cells. Interactions and processes that have been observed in different studies and cell types are here summarized in a single hypothetical animal cell. Different apoptotic stimuli may induce NO biosynthesis and the figure shows how apoptosis in animal cells may be triggered by the initial nitrosylation of GAPDH, and counteracted by several processes. For a detailed explanation, see text (Animal GAPDH: redox-dependent non-glycolytic (moonlighting) functions). GOSPEL, GAPDH’s competitor Siah1 protein enhances life; N-CoR, nuclear co-repressor; Siah1, seven in absentia homologue 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824636&req=5

Figure 8: GAPDH and apoptosis in animal cells. Interactions and processes that have been observed in different studies and cell types are here summarized in a single hypothetical animal cell. Different apoptotic stimuli may induce NO biosynthesis and the figure shows how apoptosis in animal cells may be triggered by the initial nitrosylation of GAPDH, and counteracted by several processes. For a detailed explanation, see text (Animal GAPDH: redox-dependent non-glycolytic (moonlighting) functions). GOSPEL, GAPDH’s competitor Siah1 protein enhances life; N-CoR, nuclear co-repressor; Siah1, seven in absentia homologue 1.
Mentions: Animal GAPDH is involved in the signaling cascade that governs NO-dependent apoptosis. After apoptotic stimuli, GAPDH is found in the nucleus in a number of cell systems, including neurons (Nakamura and Lipton, 2013). A fundamental prerequisite for GAPDH relocalization from the cytoplasm to the nucleus appears to be the S-nitrosylation of its catalytic cysteine. Diverse apoptotic stimuli induce NO biosynthesis in animal cells and S-nitrosylated GAPDH (SNO-GAPDH) acquires the ability to bind Siah1 (seven in absentia homologue 1), an E3-ubiquitin ligase with a nuclear localization signal (Figure 8). The SNO-GAPDH/Siah1 interaction is mediated by the C-terminal catalytic domain of GAPDH and has the effect of increasing the stability of Siah1. The complex SNO-GAPDH/Siah1 translocates to the nucleus and mediates cell death (Figure 8; Hara et al., 2005). Different mechanisms are involved in SNO-GAPDH/Siah1-mediated apoptosis (Figure 8). Diverse nuclear proteins are ubiquitinated by Siah1, including the nuclear co-repressor N-CoR (Hara et al., 2005), and SNO-GAPDH/Siah1 can also bind to acetyltransferase p300/CBP and in turn be acetylated on Lys-160. Interestingly, this interaction (in which Lys-160 of GAPDH plays an essential role) stimulates the autoacetylation of p300 and activates the acetylation of downstream targets like tumor suppressor p53 and others that, upon activation, induce cell death (Sen et al., 2008).

Bottom Line: A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation.Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells.The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Plant Redox Biology, Department of Pharmacy and Biotechnology, University of Bologna Bologna, Italy.

ABSTRACT
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme involved in glycolysis and shown, particularly in animal cells, to play additional roles in several unrelated non-metabolic processes such as control of gene expression and apoptosis. This functional versatility is regulated, in part at least, by redox post-translational modifications that alter GAPDH catalytic activity and influence the subcellular localization of the enzyme. In spite of the well established moonlighting (multifunctional) properties of animal GAPDH, little is known about non-metabolic roles of GAPDH in plants. Plant cells contain several GAPDH isoforms with different catalytic and regulatory properties, located both in the cytoplasm and in plastids, and participating in glycolysis and the Calvin-Benson cycle. A general feature of all GAPDH proteins is the presence of an acidic catalytic cysteine in the active site that is overly sensitive to oxidative modifications, including glutathionylation and S-nitrosylation. In Arabidopsis, oxidatively modified cytoplasmic GAPDH has been successfully used as a tool to investigate the role of reduced glutathione, thioredoxins and glutaredoxins in the control of different types of redox post-translational modifications. Oxidative modifications inhibit GAPDH activity, but might enable additional functions in plant cells. Mounting evidence support the concept that plant cytoplasmic GAPDH may fulfill alternative, non-metabolic functions that are triggered by redox post-translational modifications of the protein under stress conditions. The aim of this review is to detail the molecular mechanisms underlying the redox regulation of plant cytoplasmic GAPDH in the light of its crystal structure, and to provide a brief inventory of the well known redox-dependent multi-facetted properties of animal GAPDH, together with the emerging roles of oxidatively modified GAPDH in stress signaling pathways in plants.

No MeSH data available.


Related in: MedlinePlus