Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588389
Title: Regulation of E2F-1 by methylation and NEDDylation
Author: Loftus, Sarah Jane
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
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Abstract:
E2F-1 has a central role in cell cycle orchestration, and its activity is tightly regulated. One of the ways E2F-1 activity is controlled is by direct modification by post translational modifications such as acetylation, ubiquitination and phosphorylation. Here it was demonstrated that E2F-1 is targeted by two novel modifications, namely methylation by Set7/9 and NEDDylation, both within the DNA binding and heterodimerisation domain of the protein. NEDDylation and methylation of E2F-1 both decrease the stability and diminish the transcriptional activity of E2F-1. Lysine residues in E2F-1 involved in NEDDylation are also targeted by methylation, allowing the potential for interplay between these modifications. Methylation of E2F-1 was demonstrated to be a prerequisite for its NEDDylation and the multi-domain protein UHRF1 implicated in mediating this effect. The results define a new level of control on E2F-1 and suggest a protein code with pleiotropic effects involved in E2F-1 regulation.
Supervisor: La Thangue, N. B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.588389  DOI: Not available
Keywords: Cell Biology (see also Plant sciences) ; Medical Sciences ; Oncology ; Biochemistry ; post translational modification ; methylation ; NEDDylation ; Set7/9
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