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Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE193524 | GEO | 2022/11/04

REPOSITORIES: GEO

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Aberrant expression and localization of the RAP1 shelterin protein contribute to age-related phenotypes.

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Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes [2017]

Project description:Short telomeres induce a DNA damage response (DDR) that evokes apoptosis or senescence in human cells. An extant question is the contribution of this DDR to the phenotypes observed in telomeropathies. One exemplar is RAP1, a telomere-associated protein that also controls transcription at extratelomeric regions. To distinguish these roles, we generated a knock-in mouse containing a Rap1 variant unable to bind telomeres but which did not result in eroded telomeres or a DDR. Rap1 variant MEFs exhibited decreased RAP1 expression and re-localization away from telomeres, with an increased cytosolic distribution akin to that observed in aging human fibroblasts. Rap1 knock-in mice were viable, but exhibited transcriptional alterations, proinflammatory cytokine/chemokine signaling, decreased lifespans, increased body weight/fasting blood glucose levels, increased spontaneous tumor incidence, and behavioral deficits. Taken together, our data indicate that some of the underlying mechanisms that drive telomeropathies may arise from phenotypes distinct from a telomere-induced DDR.

2022-11-04 | GSE193520 | GEO

Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes [2019]

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Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes

Project description:Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes

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Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes [2017]

Project description:Aberrant expression and localization of the RAP1 shelterin protein contributes to age-related phenotypes [2017]

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TALEN gene knockouts reveal no requirement for the conserved human shelterin protein Rap1 in telomere protection and length regulation.

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TALEN gene knockouts reveal no requirement for the shelterin protein Rap1 in telomere protection and length regulation

Project description:Gene expression of human knockouts of telomere-protein Rap1 were compared to their wildtype counterparts in mutliple cell lines (available from the ATCC repository). We discovered that Rap1, desite being mostly associated with the telomere, performed a conserved role in transcriptional regulation, as evidenced by a number of genes that were differentially regulated upon deletion of Rap1.

2014-09-30 | GSE61900 | GEO