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The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways

ABSTRACT: The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways

PROVIDER: PRJNA287784 | ENA |

REPOSITORIES: ENA

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The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [BY4741]

Project description:The function of DFNA5 remained unknown for a long time, but previous functional studies by Op de Beeck et al. (2011) revealed that DFNA5 induces a growth defect in mutDFNA5- transfected HEK293T cells, as well as other cells, leading to PCD (Op de Beeck et al., 2011). The cell death-inducing capacity of DFNA5 was not only restricted to human cell lines, but was also observed in the yeast model Saccharomyces cerevisiae (Van Rossom et al., 2012). This inspired us to perform a transcriptomic analysis using two different model organisms (mammalian, HEK293T, and yeast, S.cerevisiae) to further elucidate the mechanisms related to DFNA5. Comparison of 2 transfected yeast cell populations in 2 different growth phases. In total, 4 comparisons were made, each comparison was done in duplo by a colourflip. Every conditions is represented through 2 biol reps.

2015-06-24 | E-GEOD-70168 | biostudies-arrayexpress

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [HEK293T]

Project description:The function of DFNA5 remained unknown for a long time, but previous functional studies by Op de Beeck et al. (2011) revealed that DFNA5 induces a growth defect in mutDFNA5- transfected HEK293T cells, as well as other cells, leading to PCD (Op de Beeck et al., 2011). The cell death-inducing capacity of DFNA5 was not only restricted to human cell lines, but was also observed in the yeast model Saccharomyces cerevisiae (Van Rossom et al., 2012). This inspired us to perform a transcriptomic analysis using two different model organisms (mammalian, HEK293T, and yeast, S.cerevisiae) to further elucidate the mechanisms related to DFNA5. Comparison of two HEK293T transfected cell populations, either with a WT or mutated DFNA5 gene. There are 5 biol reps for the WT transfected cells and 6 biol reps for the mut DFNA5 transfected cells.

2015-06-24 | E-GEOD-70167 | biostudies-arrayexpress

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [BY4741]

2015-06-24 | GSE70168 | GEO

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [HEK293T]

2015-06-24 | GSE70167 | GEO

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-06-24 | E-GEOD-70169 | biostudies-arrayexpress

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways.

Project description:Cell death exists in many different forms. Some are accidental, but most of them have some kind of regulation and are called programmed cell death. Programmed cell death (PCD) is a very diverse and complex mechanism and must be tightly regulated. This study investigated PCD induced by DFNA5, a gene responsible for autosomal dominant hearing loss (HL) and a tumor suppressor gene (TSG) involved in frequent forms of cancer. Mutations in DFNA5 lead to exon 8 skipping and result in HL in several families. Expression of mutant DFNA5, a cDNA construct where exon 8 is deleted, was linked to PCD both in human cell lines and in Saccharomyces cerevisiae. To further investigate the cell death mechanism induced by mutant DFNA5, we performed a microarray study in both models. We used wild-type DFNA5, which does not induce cell death, as a reference. Our data showed that the yeast pathways related to mitochondrial ATP-coupled electron transport chain, oxidative phosphorylation and energy metabolism were up-regulated, while in human cell lines, MAP kinase-related activity was up-regulated. Inhibition of this pathway was able to partially attenuate the resulting cell death induced by mutant DFNA5 in human cell lines. In yeast, the association with mitochondria was demonstrated by up-regulation of several cytochrome c oxidase (COX) genes involved in the cellular oxidative stress production. Both models show a down-regulation of protein sorting- and folding-related mechanisms suggesting an additional role for the endoplasmic reticulum (ER). The exact relationship between ER and mitochondria in DFNA5-induced cell death remains unknown at this moment, but these results suggest a potential link between the two.

| S-EPMC4504148 | biostudies-literature

The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-06-24 | GSE70169 | GEO

Saccharomyces cerevisiae

Project description:The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [BY4741]

| PRJNA287786 | ENA

Homo sapiens

Project description:The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways [HEK293T]

| PRJNA287787 | ENA

Transcriptome analysis of programmed cell death during allorecognition in Cryphonectria parasitica

Project description:Transcriptome analysis of programmed cell death during allorecognition in Cryphonectria parasitica