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Transcriptional Regulation of Oncogenic Protein Kinase Cϵ (PKCϵ) by STAT1 and Sp1 Proteins

dc.contributor.authorGutiérrez Uzquiza, Álvaro
dc.contributor.authorHongBin Wang
dc.contributor.authorRachana Garg
dc.contributor.authorBarrio Real, Laura
dc.contributor.authorMahlet B. Abera
dc.contributor.authorLopez-Haber, Cynthia
dc.contributor.authorRosemblit, Cinthia
dc.contributor.authorHuaisheng Lu
dc.contributor.authorAbba, Martin
dc.date.accessioned2024-12-16T16:37:33Z
dc.date.available2024-12-16T16:37:33Z
dc.date.issued2014-07-11
dc.description.abstractOverexpression of PKCϵ, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCϵ expression and its up-regulation in cancer, we cloned an ∼ 1.6-kb promoter segment of the human PKCϵ gene (PRKCE) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and -105 bp (region A) and -921 and -796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and -269/-247 as well as STAT1 sites in positions -880/-869 and -793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCϵ mRNA and protein expression, as well as PRKCE promoter activity. Moreover, a strong correlation was found between PKCϵ and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCϵ and its effectors in cancer therapeutics.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationHongBin Wang, Alvaro Gutierrez-Uzquiza, Rachana Garg, Laura Barrio-Real, Mahlet B. Abera, Cynthia Lopez-Haber, Cinthia Rosemblit, Huaisheng Lu, Martin Abba, Marcelo G. Kazanietz, Transcriptional Regulation of Oncogenic Protein Kinase Cϵ (PKCϵ) by STAT1 and Sp1 Proteins*, Journal of Biological Chemistry, Volume 289, Issue 28, 2014, Pages 19823-19838, https://doi.org/10.1074/jbc.M114.548446.
dc.identifier.doi10.1074/jbc.m114.548446
dc.identifier.essn0021-9258
dc.identifier.issn1083-351X
dc.identifier.officialurlhttps://doi.org/10.1074/jbc.M114.548446
dc.identifier.urihttps://hdl.handle.net/20.500.14352/112693
dc.issue.number28
dc.journal.titleJournal of Biological Chemistry
dc.language.isoeng
dc.page.final19838
dc.page.initial19823
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keywordBreast Cancer
dc.subject.keywordDiacylglycerol
dc.subject.keywordGene Expression
dc.subject.keywordProtein Kinase
dc.subject.keywordProtein Kinase C (PKCϵ)
dc.subject.keywordSTAT Transcription Factor
dc.subject.keywordSignal Transduction
dc.subject.keywordSpecificity Protein 1 (Sp1)
dc.subject.keywordTranscription Promoter
dc.subject.ucmBiología molecular (Biología)
dc.subject.unesco2403 Bioquímica
dc.titleTranscriptional Regulation of Oncogenic Protein Kinase Cϵ (PKCϵ) by STAT1 and Sp1 Proteins
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number289
dspace.entity.typePublication
relation.isAuthorOfPublicationfe7d7e09-f48f-4104-b627-5f056790b029
relation.isAuthorOfPublication.latestForDiscoveryfe7d7e09-f48f-4104-b627-5f056790b029

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Transcriptional Regulation of Oncogenic Protein Kinase Cϵ (PKCϵ) by STAT1 and Sp1 Proteins

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