Regulation of NF-κB by PML and PML-RARα

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dc.contributor.advisor O'Connor, Rosemary en
dc.contributor.advisor Carmody, Ruaidhri en
dc.contributor.author Ahmed, Abrar
dc.date.accessioned 2017-02-20T16:10:15Z
dc.date.issued 2014
dc.date.submitted 2014
dc.identifier.citation Ahmed, A. 2014. Regulation of NF-κB by PML and PML-RARα. PhD Thesis, University College Cork. en
dc.identifier.endpage 203 en
dc.identifier.uri http://hdl.handle.net/10468/3655
dc.description.abstract The 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.format.mimetype application/pdf en
dc.language English en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Abrar S. Ahmed en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject NF-κB en
dc.subject PML en
dc.subject PML en
dc.subject PML-RARα en
dc.subject p65 en
dc.title Regulation of NF-κB by PML and PML-RARα en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral Degree (Structured) en
dc.type.qualificationname PhD Scholars Programme in Cancer Biology en
dc.internal.availability Full text not available en
dc.check.info Indefinite en
dc.check.date 9999-01-01
dc.description.version Accepted Version
dc.contributor.funder Health Research Board en
dc.description.status Not peer reviewed en
dc.internal.school Biochemistry en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat E-thesis on CORA only en
ucc.workflow.supervisor r.oconnor@ucc.ie
dc.internal.conferring Spring 2015 en


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© 2014, Abrar S. Ahmed Except where otherwise noted, this item's license is described as © 2014, Abrar S. Ahmed
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