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Transcriptional regulation of human DUSP4 gene by cancer‐related transcription factors

2021Journal article Open access
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dc.contributor.authorVarela, Tatiana
dc.contributor.authorConceição, Natércia
dc.contributor.authorLaizé, Vincent
dc.contributor.authorCancela, M. Leonor
dc.date.accessioned2021-07-26T08:31:51Z
dc.date.available2021-07-26T08:31:51Z
dc.date.issued2021
dc.description.abstractDual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is responsible for the dephosphorylation and inactivation of ERK, JNK and p38, which are mitogen-activated protein kinases involved in cell proliferation, differentiation and apoptosis, but also in inflammation processes. Given its importance for cellular signalling, DUSP4 is subjected to a tight regulation and there is growing evidence that its expression is dysregulated in several tumours. However, the mechanisms underlying DUSP4 transcriptional regulation remain poorly understood. Here, we analysed the regulation of the human DUSP4 promoters 1 and 2, located upstream of exons 1 and 2, respectively, by the cancer-related transcription factors (TFs) STAT3, FOXA1, CTCF and YY1. The presence of binding sites for these TFs was predicted in both promoters through the in silico analysis of DUSP4, and their functionality was assessed through luciferase activity assays. Regulatory activity of the TFs tested was found to be promoter-specific. While CTCF stimulated the activity of promoter 2 that controls the transcription of variants 2 and X1, STAT3 stimulated the activity of promoter 1 that controls the transcription of variant 1. YY1 positively regulated both promoters, although to different extents. Through site-directed mutagenesis, the functionality of YY1 binding sites present in promoter 2 was confirmed. This study provides novel insights into the transcriptional regulation of DUSP4, contributing to a better comprehension of the mechanisms of its dysregulation observed in several types of cancer.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1002/jcb.30078pt_PT
dc.identifier.issn0730-2312
dc.identifier.urihttp://hdl.handle.net/10400.1/16811
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationAlgarve Centre for Marine Sciences
dc.relationIdentification of novel CDKL5 molecular targets/pathways associated with skeletal defects present in CDKL5 associated disorders
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCTCFpt_PT
dc.subjectDUSP4pt_PT
dc.subjectFOXA1pt_PT
dc.subjectSTAT3pt_PT
dc.subjectTranscriptional regulationpt_PT
dc.subjectYY1pt_PT
dc.titleTranscriptional regulation of human DUSP4 gene by cancer‐related transcription factorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleIdentification of novel CDKL5 molecular targets/pathways associated with skeletal defects present in CDKL5 associated disorders
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F144230%2F2019/PT
oaire.citation.titleJournal of Cellular Biochemistrypt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
person.familyNameVarela
person.familyNameConceição
person.familyNameLaizé
person.familyNameCancela
person.givenNameTatiana da Conceição Domingos
person.givenNameNatércia
person.givenNameVincent
person.givenNameM. Leonor
person.identifier.ciencia-idF613-7482-6731
person.identifier.ciencia-id7C11-760D-F425
person.identifier.orcid0000-0002-5057-0912
person.identifier.orcid0000-0001-9565-9198
person.identifier.orcid0000-0003-3114-6662
person.identifier.ridB-4463-2008
person.identifier.scopus-author-id6602982778
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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