Regulation of p110delta PI 3-kinase gene expression.

<h4>Background</h4>Despite an intense interest in the biological functions of the phosphoinositide 3-kinase (PI3K) signalling enzymes, little is known about the regulation of PI3K gene expression. This also applies to the leukocyte-enriched p110delta catalytic subunit of PI3K, an enzyme...

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Autores principales:	Klaartje Kok, Gemma E Nock, Elizabeth A G Verrall, Michael P Mitchell, Daan W Hommes, Maikel P Peppelenbosch, Bart Vanhaesebroeck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98fb8eccf7e840f2886d4059e2fbc113
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spelling	oai:doaj.org-article:98fb8eccf7e840f2886d4059e2fbc1132021-11-25T06:16:13ZRegulation of p110delta PI 3-kinase gene expression.1932-620310.1371/journal.pone.0005145https://doaj.org/article/98fb8eccf7e840f2886d4059e2fbc1132009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19357769/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Despite an intense interest in the biological functions of the phosphoinositide 3-kinase (PI3K) signalling enzymes, little is known about the regulation of PI3K gene expression. This also applies to the leukocyte-enriched p110delta catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy.<h4>Principal findings</h4>We show that p110delta expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110delta gene transcription appears to be constitutive and not subject to acute stimulation. 5'RACE experiments revealed that p110delta mRNA transcripts contain distinct upstream untranslated exons (named exon -1, -2a, -2b, -2c and -2d), which are located up to 81 kb upstream of the translational start codon in exon 1. The levels of all the different p110delta transcripts are higher in leukocytes compared to non-leukocytes, with the p110delta transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110delta gene which has enhanced promoter activity in leukocytes compared to non-leukocytes. In human, this TF cluster is located immediately upstream of exon -2a whilst in mouse, it is located within exon -2a.<h4>Conclusion</h4>This study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110delta.Klaartje KokGemma E NockElizabeth A G VerrallMichael P MitchellDaan W HommesMaikel P PeppelenboschBart VanhaesebroeckPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5145 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Klaartje Kok Gemma E Nock Elizabeth A G Verrall Michael P Mitchell Daan W Hommes Maikel P Peppelenbosch Bart Vanhaesebroeck Regulation of p110delta PI 3-kinase gene expression.
description	<h4>Background</h4>Despite an intense interest in the biological functions of the phosphoinositide 3-kinase (PI3K) signalling enzymes, little is known about the regulation of PI3K gene expression. This also applies to the leukocyte-enriched p110delta catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy.<h4>Principal findings</h4>We show that p110delta expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110delta gene transcription appears to be constitutive and not subject to acute stimulation. 5'RACE experiments revealed that p110delta mRNA transcripts contain distinct upstream untranslated exons (named exon -1, -2a, -2b, -2c and -2d), which are located up to 81 kb upstream of the translational start codon in exon 1. The levels of all the different p110delta transcripts are higher in leukocytes compared to non-leukocytes, with the p110delta transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110delta gene which has enhanced promoter activity in leukocytes compared to non-leukocytes. In human, this TF cluster is located immediately upstream of exon -2a whilst in mouse, it is located within exon -2a.<h4>Conclusion</h4>This study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110delta.
format	article
author	Klaartje Kok Gemma E Nock Elizabeth A G Verrall Michael P Mitchell Daan W Hommes Maikel P Peppelenbosch Bart Vanhaesebroeck
author_facet	Klaartje Kok Gemma E Nock Elizabeth A G Verrall Michael P Mitchell Daan W Hommes Maikel P Peppelenbosch Bart Vanhaesebroeck
author_sort	Klaartje Kok
title	Regulation of p110delta PI 3-kinase gene expression.
title_short	Regulation of p110delta PI 3-kinase gene expression.
title_full	Regulation of p110delta PI 3-kinase gene expression.
title_fullStr	Regulation of p110delta PI 3-kinase gene expression.
title_full_unstemmed	Regulation of p110delta PI 3-kinase gene expression.
title_sort	regulation of p110delta pi 3-kinase gene expression.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/98fb8eccf7e840f2886d4059e2fbc113
work_keys_str_mv	AT klaartjekok regulationofp110deltapi3kinasegeneexpression AT gemmaenock regulationofp110deltapi3kinasegeneexpression AT elizabethagverrall regulationofp110deltapi3kinasegeneexpression AT michaelpmitchell regulationofp110deltapi3kinasegeneexpression AT daanwhommes regulationofp110deltapi3kinasegeneexpression AT maikelppeppelenbosch regulationofp110deltapi3kinasegeneexpression AT bartvanhaesebroeck regulationofp110deltapi3kinasegeneexpression
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Regulation of p110delta PI 3-kinase gene expression.

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