Cargando…

SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A

Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In th...

Descripción completa

Detalles Bibliográficos
Autores principales: Rhee, Dong Keun, Hockman, Steven C., Choi, Sunkyung, Kim, Yong-Eun, Park, Chungoo, Manganiello, Vincent C., Kim, Kee K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548871/
https://www.ncbi.nlm.nih.gov/pubmed/28743736
http://dx.doi.org/10.1042/BSR20170975
_version_ 1783255897441566720
author Rhee, Dong Keun
Hockman, Steven C.
Choi, Sunkyung
Kim, Yong-Eun
Park, Chungoo
Manganiello, Vincent C.
Kim, Kee K.
author_facet Rhee, Dong Keun
Hockman, Steven C.
Choi, Sunkyung
Kim, Yong-Eun
Park, Chungoo
Manganiello, Vincent C.
Kim, Kee K.
author_sort Rhee, Dong Keun
collection PubMed
description Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In the present study, we investigated the transcriptional regulation of PDE3A, and found that the splicing factor proline- and glutamine-rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5′-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A-TSSs using ChIP sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A. In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared with normal cervical tissue. Furthermore, overexpression of PDE3A induced sensitivity to anticancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity, offering a novel molecular target for the development of anticancer therapies.
format Online
Article
Text
id pubmed-5548871
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-55488712017-08-24 SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A Rhee, Dong Keun Hockman, Steven C. Choi, Sunkyung Kim, Yong-Eun Park, Chungoo Manganiello, Vincent C. Kim, Kee K. Biosci Rep Research Articles Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In the present study, we investigated the transcriptional regulation of PDE3A, and found that the splicing factor proline- and glutamine-rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5′-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A-TSSs using ChIP sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A. In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared with normal cervical tissue. Furthermore, overexpression of PDE3A induced sensitivity to anticancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity, offering a novel molecular target for the development of anticancer therapies. Portland Press Ltd. 2017-08-09 /pmc/articles/PMC5548871/ /pubmed/28743736 http://dx.doi.org/10.1042/BSR20170975 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Rhee, Dong Keun
Hockman, Steven C.
Choi, Sunkyung
Kim, Yong-Eun
Park, Chungoo
Manganiello, Vincent C.
Kim, Kee K.
SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title_full SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title_fullStr SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title_full_unstemmed SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title_short SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A
title_sort sfpq, a multifunctional nuclear protein, regulates the transcription of pde3a
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548871/
https://www.ncbi.nlm.nih.gov/pubmed/28743736
http://dx.doi.org/10.1042/BSR20170975
work_keys_str_mv AT rheedongkeun sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT hockmanstevenc sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT choisunkyung sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT kimyongeun sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT parkchungoo sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT manganiellovincentc sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a
AT kimkeek sfpqamultifunctionalnuclearproteinregulatesthetranscriptionofpde3a