GAPDH: A common enzyme with uncommon functions

Nicholls, Craig; Li, He; Liu, Junping

doi:10.1111/j.1440-1681.2011.05599.x

Cited by 234 publications

(208 citation statements)

References 73 publications

(115 reference statements)

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“…2), and influences the stability, location, and function of a variety of RNA species through direct interactions (reviewed in ref. 24), we examined whether an interaction between GAPDH and the telomerase RNA moiety hTERC exists. As a positive control for GAPDH RNA binding, an AU-rich RNA molecule (4× AUUUA) was used, as has been previously demonstrated to interact with GAPDH (26).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, studies have shown that GAPDH binds to telomeres directly (8,9). These findings suggest that while catalyzing energy production, GAPDH also regulates chromosome stability and genome integrity by multiple mechanisms, including the maintainance of telomere homeostasis to facilitate longevity of cell proliferation (24). However, the mechanisms by which GAPDH is involved in telomere homeostasis are not known, and whether or not the regulation of telomere length by GADPH is dependent on telomerase requires further investigation.…”

mentioning

confidence: 90%

“…Intriguingly as a gene encoding a single 38-kDa protein without alternate splicing, GAPDH displays multiple functions that are independent of its role in energy generation (reviewed in refs. 5,[22][23][24]. A large body of evidence indicates that GAPDH responds to various stress insults by translocation to the nucleus (3)(4)(5)(6)(7)25).…”

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confidence: 99%

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

Nicholls

Pinto

et al. 2012

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

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Oxidative stress regulates telomere homeostasis and cellular aging by unclear mechanisms. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key mediator of many oxidative stress responses, involving GAPDH nuclear translocation and induction of cell death. We report here that GAPDH interacts with the telomerase RNA component (TERC), inhibits telomerase activity, and induces telomere shortening and breast cancer cell senescence. The Rossmann fold containing NAD + binding region on GAPDH is responsible for the interaction with TERC, whereas a lysine residue in the GAPDH catalytic domain is required for inhibiting telomerase activity and disrupting telomere maintenance. Furthermore, the GAPDH substrate glyceraldehyde-3-phosphate (G3P) and the nitric oxide donor S-nitrosoglutathione (GSNO) both negatively regulate GAPDH inhibition of telomerase activity. Thus, we demonstrate that GAPDH is regulated to target the telomerase complex, resulting in an arrest of telomere maintenance and cancer cell proliferation. and apoptosis. Although production of daughter cells costs energy, it remains largely elusive how energy metabolism regulates normal cell aging and lifespan. Considerable evidence suggests that metabolic waste causes premature senescence and apoptosis, shortening cellular lifespan. Accumulation of reactive oxygen species (ROS) damages cellular enzymes, organelle membranes, and chromosomal DNA including telomeres (the ends of chromosomes) (1, 2). Whereas enzymes that reduce the production of metabolic hazards may operate to extend cellular lifespan, recent studies demonstrate that the energy producing enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that limits ROS production undergoes structural modifications and travel into the nucleus (3-7) to interact with telomeres directly and to potentially alleviate stress-induced cell aging (8, 9).Human telomeres are composed of arrays of a few thousand tandem DNA repeats of TTAGGG and various binding proteins. Telomeres undergo progressive shortening as somatic cells divide, due to the inability of cells to replicate the extreme ends of chromosomes. When telomeres are critically short, cells exit the cell cycle and undergo cell senescence (10-13). As a measure to maintain telomeres for continuous renewal of germ lines, development of embryonic stem cells, clonal expansion of lymphocytes, and immortalization of neoplastic cells, telomerase is activated to synthesize and maintain telomeres by reverse transcription (10-13).Telomerase is a large ribonucleoprotein complex containing the catalytic subunit telomerase reverse transcriptase (TERT) and an RNA template (reviewed in refs. 13 and 14). Human telomerase reverse transcriptase (hTERT) comprises 1,132 amino acid residues and human telomerase RNA (hTERC) is composed of 451 nucleotides (15-18). Reconstitution of telomerase activity in telomerase-negative cells can be achieved by expression of hTERT, demonstrating that hTERT is the rate-limiting component of the enzyme complex (19,20).GAPDH has long been recognize...

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Section: Resultsmentioning

confidence: 99%

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confidence: 90%

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

Nicholls

Pinto

et al. 2012

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

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“…Among those, there are genes related to synthesis, degradation, and transport of proteins, such as Ubiquitin, RPLP0 (ribosomal protein, large, P0), HPRT (hypoxanthine-guanine phosphoribosyltransferase) and 18S rRNA (Hochstrasser, 2009), in addition to others related to the transport of electrons and the respiratory chain, such as the GAPDH (glyceraldehyde 3-phosphate dehydrogenase) gene (Nicholls et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

SHORT-COMMUNICATION Evaluation of perfused bovine udder for gene expression studies in dairy cows

Pinto

Fonseca²,

Brandão

et al. 2017

Genet. Mol. Res.

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ABSTRACT. Intramammary infections are one of the main causes of productivity loss in dairy cows. To better understand the immune system response and to avoid the use of live animals, we validated the use of isolated bovine udder as an ex situ model. Six mammary glands were collected from cows ready for culling. Three udders were perfused with Tyrode's solution and three were not-perfused. During six hours, we collected perfusate samples for biochemical analysis. We also collected alveolar and teat canal tissue to evaluate gene expression. The biochemical parameters indicated that the perfused udders remained viable for the entire period of the experiment. A real-time polymerase chain reaction showed an increase in 18S rRNA gene expression in the alveolar tissue at 3 and 4 h after perfusion. There was also an increase in the Ubiquitin gene in the teat canal from not-perfused udders at 1, 3, and 4 h after slaughter. In general, gene expression was stable during the experiment. Our results indicated that the isolated perfused bovine udder model is appropriate for genetic studies, opening a new perspective in animal experimentation methods.

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“…Nonetheless, expression levels of the housekeeping genes may also vary considerably under certain circumstances because they can be involved in processes other than maintenance functions of the cell, e.g. apoptosis (Nicholls, Li & Liu, 2012), cytokinesis (D'Souza Schorey & Chavrier, 2006) and development .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of potential reference genes for real-time qPCR analysis in a biparental beetle, Lethrus apterus (Coleoptera: Geotrupidae)

Nagy

Németh

Juhász

et al. 2017

Preprint

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Hormones play an important role in the regulation of physiological, developmental and behavioural processes. Many of these mechanisms in insects, however, are still not well understood. One way to investigate hormonal regulation is to analyse gene expression patterns of hormones and their receptors in question by real-time quantitative polymerase chain reaction (RT-qPCR). This method, however, requires stably expressed reference genes for normalisation. In the present study, we evaluated 11 candidate housekeeping genes as reference genes in samples of Lethrus apterus, an earth-boring beetle with biparental care, collected from a natural population. For identifying the most stable genes we used the following computational methods: geNorm, NormFinder, BestKeeper, comparative delta Ct method and RefFinder. Based on our results, the two body regions sampled (head and thorax) differ in which genes are most stably expressed. We identified two candidate reference genes for each region investigated: ribosomal protein L7A and RP18 in samples extracted from the head, and ribosomal protein L7A and RP4 extracted from the muscles of the thorax. These reference genes can be used to study the hormonal regulation of reproduction and parental care in Lethrus apterus in the future. In the present study, we evaluated 11 candidate housekeeping genes as reference genes in samples of Lethrus apterus, an earth boring beetle with biparental care, collected from a natural population. For identifying the most stable genes we used the following computational methods: geNorm, NormFinder, BestKeeper, comparative delta Ct method and RefFinder. Based on our results, the two body regions sampled (head and thorax) differ in which genes are most stably expressed. We identified two candidate reference genes for each region investigated: ribosomal protein L7A and RP18 in samples extracted from the head, and ribosomal protein L7A and RP4 extracted from the muscles of the thorax. These reference genes can be used to study the hormonal regulation of reproduction and parental care in Lethrus apterus in the future.

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GAPDH: A common enzyme with uncommon functions

Cited by 234 publications

References 73 publications

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

SHORT-COMMUNICATION Evaluation of perfused bovine udder for gene expression studies in dairy cows

Evaluation of potential reference genes for real-time qPCR analysis in a biparental beetle, Lethrus apterus (Coleoptera: Geotrupidae)

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