In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53

Zannat, Mst. Thangima; Bhattacharjee, Rumpa Biswas; Bag, Jnanankur

doi:10.1016/j.bbrc.2011.04.094

Cited by 15 publications

(15 citation statements)

References 23 publications

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“…Recent studies underscored the role of GAPDH in apoptosis and OS, possibly due to its propensity for nuclear translocation (Dastoor and Dreyer, 2001; Sukhanov et al , 2006; Thangima Zannat et al , 2011). Additionally, GAPDH activity was found to decline upon exposure to doxorubicin (a chemotherapeutic drug), directly correlating with a decline in ATP levels (Wolf and Baynes, 2006).…”

Section: Resultsmentioning

confidence: 99%

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

2013

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Extracellular human immunodeficiency virus type type 1 (HIV-1) viral protein R (Vpr) is a pleiotropic protein accomplishing several functions within the viral life cycle. While Vpr has been described extensively as an intracellular protein, very little is known about its role as an extracellular protein. In fact, HIV-1 Vpr has been detected in the blood, serum, and cerebrospinal fluid of HIV-1-infected patients, with concentrations increasingly higher in late-stage disease. To determine the role exogenous Vpr plays in HIV-associated central nervous system dysfunction, primary human fetal astrocytes were exposed to recombinant Vpr and a time- and dose-dependent decrease was demonstrated in two fundamental intracellular metabolites (ATP and glutathione (GSH)). Additionally, exposure to exogenous Vpr led to increased caspase activity and secretion of proinflammatory cytokines IL-6 and IL-8 and chemoattractants, monocyte chemotactic protein-1 and migration inhibition factor. Extracellular Vpr also dampened the glycolytic pathway through impairment of GAPDH activity, causing a decline in the levels of ATP. The reduction in intracellular ATP increased reactive oxygen species buildup, decreasing GSH concentrations, which affected several genes in the oxidative stress pathway. In addition, exposure of the SK-N-SH neuroblastoma cell line to conditioned medium from exogenous Vpr-treated astrocytes decreased synthesis of GSH, leading to their apoptosis. These observations point to a role that Vpr plays in altering astrocytic metabolism and indirectly affecting neuronal survival. We propose a model that may explain some of the neurological damage and therefore neurocognitive impairment observed during the course of HIV-1 disease.

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Section: Resultsmentioning

confidence: 99%

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

2013

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“…(A) Total RNA was extracted following 66 h of transfection with SiRNA and from non transfected (NT) cells and poly(A) tail length was analyzed by PAT assay as described by Salles et al 1999 [23] with β-actin specific primers. The PCR product was analyzed in 1% agarose gel.…”

Section: Resultsmentioning

confidence: 99%

“…Western blotting, immunostaining, and in situ hybridization were performed as described previously [22], [23]. After immunostaining with PABP4 antibody, the nuclei of the cells were further stained with DAPI (Santa Cruz Biotechnology, CA, USA) (0.5 µg/µl) for 10 min, washed twice with PBS and mounted onto slides.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoprecipitation was done as previously described [23] with the following modifications. Following 72 h of transfection, cells grown in 60 mm plate were lysed in 400 µl of chilled PLC buffer (10% glycerol, 50 mM Hepes–HCl, pH 7.5, 150 mM NaCl, 1.5 mM MgCl 2 , 1 mM EGTA, 100 mM NaPPi, 100 mM NaF, and 1% Triton X-100) by gentle sonication using XL2020 Sonicator (Mandel Scientific) at setting 1, pulse 3 (4 s each) to break the cytoplasmic membrane.…”

Section: Methodsmentioning

confidence: 99%

“…The precipitated RNA was collected by centrifugation at 10,000 g for 10 min at 4°C and resuspended in RNAse free water. Contaminating DNA was removed from RNA samples by RQ1 RNase-free DNAse (Promega) treatment prior to being reverse transcribed and PCR amplified using β-actin pre-mRNA primers [23]. For IP with PABPN1, 30 cycles of amplification were used, whereas for IP with PABP4 40 cycles were used.…”

Section: Methodsmentioning

confidence: 99%

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Depletion of Nuclear Poly(A) Binding Protein PABPN1 Produces a Compensatory Response by Cytoplasmic PABP4 and PABP5 in Cultured Human Cells

Bhattacharjee

Bag

2012

PLoS ONE

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BackgroundIn vertebrates, poly(A) binding protein (PABP) is known to exist in five different isoforms. PABPs are primarily cytosolic with the exception of the nuclear PABP (PABPN1), which is located in the nucleus. Within the nucleus, PABPN1 is believed to bind to the poly(A) tail of nascent mRNA and along with cleavage and polyadenylation specificity factor (CPSF) define the length of the newly synthesized poly(A) tail.Methodology/Principal FindingsThe cellular role of PABP1 has been extensively studied over the years; however, the function of other PABPs remains poorly defined. In order to understand the role of PABPN1 in cellular mRNA metabolism and it’s interrelation with other PABPs, we depleted PABPN1 using RNAi in HeLa and HEK293 cells. Our results show that PABPN1 depletion did not have any effect on the poly(A) tail length, nuclear export of mRNA, mRNA translation, and transcription. Rather, PABPN1 depletion resulted in a compensatory response as observed by increased level of PABP5 and nuclear accumulation of PABP4. In addition, PABP4 was associated with the poly(A) tract of pre-mRNA and CPSF in PABPN1 depleted cells. Nevertheless, PABPN1 depletion significantly affected cell survival as evidenced by an increase in apoptosis markers: phosphorylated p53 and PUMA and as judged by the expression of ER stress marker GRP78.ConclusionOur results suggest that although function of PABPN1 may be compensated by nuclear translocation of PABP4 and perhaps by increase in the cytoplasmic abundance of PABP5, these were not sufficient to prevent apoptosis of cells. Thus PABPN1 may have a novel anti apoptotic role in mammalian cells.

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Protein acetylation in the critical biological processes in protozoan parasites

Maran

Fleck

Monteiro-Teles

et al. 2021

Trends in Parasitology

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In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53

Cited by 15 publications

References 23 publications

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

Depletion of Nuclear Poly(A) Binding Protein PABPN1 Produces a Compensatory Response by Cytoplasmic PABP4 and PABP5 in Cultured Human Cells

Protein acetylation in the critical biological processes in protozoan parasites

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