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Title: Cell cycle dependent post-translational modifications during development
Author: Daniels, M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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Cell fate choice is a complex process that involves several successive steps and signalling events, integrated and co-ordinated with proliferation. Particular combinations of transcription factors (TFs) are involved in this complex program and post-translational modifications of TFs largely play a key role in this. In this thesis, the role of a negative co-factor of TFs, inhibitor of differentiation (Id), and its regulation by the cyclin dependent kinase (cdk) are investigated. Id3 effectively antagonises the activities of proneural basic helix-loop-helix TFs by interacting with them and leading to an enhancement of their degradation. This inhibitory activity was significantly increased by in a modified Id3 that cannot be phosphorylated by cdk. Id3 is also shown to interact with histone de-acetylase, and possibly control the accessibility of TFs to their target promoter regions. The cdk inhibitors also influence cell fate choice as well as inhibition of cell cycle progression. Characterisation of two novel cdk inhibitors was performed, and found to induce glial cells in the retina. The mechanism of SUMOylation was explored, since SUMO is required for mitotic growth and cell viability, in the context of development. The expression patterns of Xenopus SUMO genes and SUMO-regulatory molecules isolated from the EST database were examined in this thesis. In addition, the novel role of SUMO E3 ligase, PIASya, on mesoderm induction is discussed. In addition to SUMOylating Smad2, PIASya was found to inhibit transcriptional activity of Smad2 by direct interaction and this is not SUMOylation-dependent. This thesis demonstrates that cell cycle dependent post-translational modifications of TFs affect cell fate by a complex network of signalling pathways. These findings may be relevant to tumourgenesis as well as development since the co-ordination of the cell cycle with cellular differentiation is at the heart of both processes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available