A study of the regulation of Trib family members expression in normal and malignant haematopoiesis

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dc.contributor.advisor McCarthy, Tommie V. en
dc.contributor.advisor Keeshan, Karen en
dc.contributor.author Hannon, Maura
dc.date.accessioned 2014-11-14T15:55:58Z
dc.date.issued 2014
dc.date.submitted 2014
dc.identifier.citation Hannon, M. 2014. A study of the regulation of Trib family members expression in normal and malignant haematopoiesis. PhD Thesis, University College Cork. en
dc.identifier.endpage 330
dc.identifier.uri http://hdl.handle.net/10468/1708
dc.description.abstract The Tribbles family of genes consist of three members; TRIB1, TRIB2 and TRIB3. Trib1 and Trib2 have been identified as oncogenes that can induce AML in mice. However little is known about how the expressions of the Tribbles family genes are controlled in the cell during haematopoiesis or leukaemogenesis. To investigate the Tribbles genes in leukaemia a bioinformatics approach was used. TRIB2 expression was found to be elevated in T-ALL and ALL with t(1;19). TRIB1 was found not to be significantly elevated in any leukaemic subtypes. Analyses of the TRIB1 and TRIB2 gene signatures in both leukaemic and normal haematopoietic cells identified pathways and transcription factors associated with these signatures. Pathways enriched for the TRIB1 signature included TLR signalling pathways and NF-κB pathways. Transcription factors enriched for this signature include C/EBP and SRF. Enriched for the TRIB2 signature includes T cell signalling pathways and Notch signalling pathways. Transcription factors enriched for this signature include E2F and ETS. Further investigation in vitro confirmed the finding that E2F1 was as a potential regulator of TRIB2 expression. E2F1 is able to directly bind to the TRIB2 promoter region and induce TRIB2 expression. C/EBPα p42 was found to inhibit E2F1 and the p30 isoform was found to cooperate with E2F1 induced activation of the TRIB2 promoter. Indicating the potential presence of a regulatory loop involved in the regulation of the TRIB2 gene. In conclusion we have investigated the Tribbles gene signatures in both normal haematopoietic and leukaemic cells. This has led to the identification of a number of pathways and transcription factors associated with these genes. We have also identified a family of transcription factors directly responsible for the regulation of TRIB2 expression. This regulatory pathway has the potential to be targeted in the treatment of leukaemia with a high TRIB2 signature. en
dc.description.sponsorship European Commission (Marie Curie Actions) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Maura Hannon. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Tribbles en
dc.subject TRIB1 en
dc.subject TRIB2 en
dc.subject TRIB3 en
dc.subject Haematopoiesis en
dc.subject Leukaemia en
dc.title A study of the regulation of Trib family members expression in normal and malignant haematopoiesis en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text not available en
dc.check.info Restricted to everyone for five years en
dc.check.date 2019-11-13T15:55:58Z
dc.description.version Accepted Version
dc.contributor.funder Irish Research Council en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder European Commission 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 Both hard copy thesis and e-thesis en
ucc.workflow.supervisor t.mccarthy@ucc.ie
dc.internal.conferring Summer Conferring 2014

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© 2014, Maura Hannon. Except where otherwise noted, this item's license is described as © 2014, Maura Hannon.
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