Gene expression profiling in cells with enhanced gamma-secretase activity.

<h4>Background</h4>Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular an...

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Autores principales:	Alexandra I Magold, Matthias Cacquevel, Patrick C Fraering
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2270edeb0fc445ebaaf1b69e9999bf2d
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spelling	oai:doaj.org-article:2270edeb0fc445ebaaf1b69e9999bf2d2021-11-25T06:20:17ZGene expression profiling in cells with enhanced gamma-secretase activity.1932-620310.1371/journal.pone.0006952https://doaj.org/article/2270edeb0fc445ebaaf1b69e9999bf2d2009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19763259/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of gamma-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of gamma-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways.<h4>Methodology/principal findings</h4>To identify genes and molecular functions transcriptionally affected by gamma-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited gamma-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to gamma-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by gamma-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices.<h4>Conclusions/significance</h4>Investigating the effects of gamma-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of gamma-secretase and its roles in cancer and Alzheimer's disease pathology.Alexandra I MagoldMatthias CacquevelPatrick C FraeringPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 9, p e6952 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexandra I Magold Matthias Cacquevel Patrick C Fraering Gene expression profiling in cells with enhanced gamma-secretase activity.
description	<h4>Background</h4>Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of gamma-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of gamma-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways.<h4>Methodology/principal findings</h4>To identify genes and molecular functions transcriptionally affected by gamma-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited gamma-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to gamma-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by gamma-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices.<h4>Conclusions/significance</h4>Investigating the effects of gamma-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of gamma-secretase and its roles in cancer and Alzheimer's disease pathology.
format	article
author	Alexandra I Magold Matthias Cacquevel Patrick C Fraering
author_facet	Alexandra I Magold Matthias Cacquevel Patrick C Fraering
author_sort	Alexandra I Magold
title	Gene expression profiling in cells with enhanced gamma-secretase activity.
title_short	Gene expression profiling in cells with enhanced gamma-secretase activity.
title_full	Gene expression profiling in cells with enhanced gamma-secretase activity.
title_fullStr	Gene expression profiling in cells with enhanced gamma-secretase activity.
title_full_unstemmed	Gene expression profiling in cells with enhanced gamma-secretase activity.
title_sort	gene expression profiling in cells with enhanced gamma-secretase activity.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/2270edeb0fc445ebaaf1b69e9999bf2d
work_keys_str_mv	AT alexandraimagold geneexpressionprofilingincellswithenhancedgammasecretaseactivity AT matthiascacquevel geneexpressionprofilingincellswithenhancedgammasecretaseactivity AT patrickcfraering geneexpressionprofilingincellswithenhancedgammasecretaseactivity
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Gene expression profiling in cells with enhanced gamma-secretase activity.

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