Regulation of NF-κB by PML and PML-RARα

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dc.check.date9999-01-01
dc.check.embargoformatE-thesis on CORA onlyen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoIndefiniteen
dc.check.opt-outNoen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorO'Connor, Rosemaryen
dc.contributor.advisorCarmody, Ruaidhrien
dc.contributor.authorAhmed, Abrar
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2017-02-20T16:10:15Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThe transcription factor NF-κB is the master regulator of the immune response but also acts broadly to regulate gene expression that influences cell survival, proliferation and differentiation. Post-translational modification of NF-κB, phosphorylation in particular, is essential for the transactivation activity of NF-κB. Promyelocytic Leukemia (PML) is a nuclear protein that forms nuclear bodies (PML NBs), sub-nuclear structures that are associated with transcriptionally active genomic regions that have been implicated in multiple processes such as apoptosis, senescence and anti-viral responses. A significant proportion of PML protein is not bound by NBs and there is limited literature to separate the function of diffused PML and PML NBs. Chromosomal translocations leading to the expression of a PML-retinoic acid receptor-α (PML/RARα) fusion protein are causative for acute promyelocytic leukemia (APL). We demonstrate that sumoylation of PML and PML NBs isinvovled in NF-κB- induced transcriptional responses and is required for phosphorylation of NF-κB p65. This is the first study to separate the function of diffused PML and PML NBs. Additionally, our analysis of available transcriptional profiles of all-trans retinoic acid treated APL cells identifies a NF-κB transcriptional programme suppressed by PML/RARα. We further demonstrate that PML/RARα inhibits NF-κB phosphorylation and transcriptional activity. Our findings establish an important role for PML in promoting NF-κB transcriptional activity which may contribute to APL initiation and maintenance. Together, our findings demonstrate a critical role for PML in supporting NF-κB post-translational modification and transcriptional activity and identify a PML/RARα suppressed NF-κB transcriptional programme which may be relevant to the pathogenesis of APL.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAhmed, A. 2014. Regulation of NF-κB by PML and PML-RARα. PhD Thesis, University College Cork.en
dc.identifier.endpage203en
dc.identifier.urihttps://hdl.handle.net/10468/3655
dc.languageEnglishen
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Abrar S. Ahmeden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectNF-κBen
dc.subjectPMLen
dc.subjectPMLen
dc.subjectPML-RARαen
dc.subjectp65en
dc.thesis.opt-outfalse
dc.titleRegulation of NF-κB by PML and PML-RARαen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoral Degree (Structured)en
dc.type.qualificationnamePhD Scholars Programme in Cancer Biologyen
ucc.workflow.supervisorr.oconnor@ucc.ie
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