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Regulation of p110δ PI 3-Kinase Gene Expression
BACKGROUND: 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 p110δ catalytic subunit of PI3K, an enzyme that has attracted wide...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663053/ https://www.ncbi.nlm.nih.gov/pubmed/19357769 http://dx.doi.org/10.1371/journal.pone.0005145 |
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author | Kok, Klaartje Nock, Gemma E. Verrall, Elizabeth A. G. Mitchell, Michael P. Hommes, Daan W. Peppelenbosch, Maikel P. Vanhaesebroeck, Bart |
author_facet | Kok, Klaartje Nock, Gemma E. Verrall, Elizabeth A. G. Mitchell, Michael P. Hommes, Daan W. Peppelenbosch, Maikel P. Vanhaesebroeck, Bart |
author_sort | Kok, Klaartje |
collection | PubMed |
description | BACKGROUND: 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 p110δ catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy. PRINCIPAL FINDINGS: We show that p110δ expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110δ gene transcription appears to be constitutive and not subject to acute stimulation. 5′RACE experiments revealed that p110δ 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 p110δ transcripts are higher in leukocytes compared to non-leukocytes, with the p110δ transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110δ 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. CONCLUSION: This study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110δ. |
format | Text |
id | pubmed-2663053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26630532009-04-09 Regulation of p110δ PI 3-Kinase Gene Expression Kok, Klaartje Nock, Gemma E. Verrall, Elizabeth A. G. Mitchell, Michael P. Hommes, Daan W. Peppelenbosch, Maikel P. Vanhaesebroeck, Bart PLoS One Research Article BACKGROUND: 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 p110δ catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy. PRINCIPAL FINDINGS: We show that p110δ expression is mainly regulated at the transcriptional level. In fibroblasts, lymphocytes and myeloid cells, p110δ gene transcription appears to be constitutive and not subject to acute stimulation. 5′RACE experiments revealed that p110δ 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 p110δ transcripts are higher in leukocytes compared to non-leukocytes, with the p110δ transcript containing exon -2a most abundantly expressed. We have identified a highly conserved transcription factor (TF) binding cluster in the p110δ 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. CONCLUSION: This study identifies a conserved PIK3CD promoter region that may account for the predominant leukocyte expression of p110δ. Public Library of Science 2009-04-09 /pmc/articles/PMC2663053/ /pubmed/19357769 http://dx.doi.org/10.1371/journal.pone.0005145 Text en Kok et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kok, Klaartje Nock, Gemma E. Verrall, Elizabeth A. G. Mitchell, Michael P. Hommes, Daan W. Peppelenbosch, Maikel P. Vanhaesebroeck, Bart Regulation of p110δ PI 3-Kinase Gene Expression |
title | Regulation of p110δ PI 3-Kinase Gene Expression |
title_full | Regulation of p110δ PI 3-Kinase Gene Expression |
title_fullStr | Regulation of p110δ PI 3-Kinase Gene Expression |
title_full_unstemmed | Regulation of p110δ PI 3-Kinase Gene Expression |
title_short | Regulation of p110δ PI 3-Kinase Gene Expression |
title_sort | regulation of p110δ pi 3-kinase gene expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663053/ https://www.ncbi.nlm.nih.gov/pubmed/19357769 http://dx.doi.org/10.1371/journal.pone.0005145 |
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