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Title: The role of fission yeast F-box protein Pof1 in cell growth control
Author: Harrison, Clare Louise
ISNI:       0000 0001 3538 6466
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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The ubiquitin-proteasome pathway is a central mechanism for regulating protein stability in eukaryotic cells. It involves the attachment of ubiquitin to a target protein marking it for degradation by the 26S proteasome. E3 ubiquitin ligases are an essential part of this process and one of the largest and most variable E3 ligase families is that of the SCF complexes. In order to study the role of the SCF complex in fission yeast, the role of Pof1, an essential fission yeast F-box protein, has been characterised. Temperature-sensitive pof1 mutants were generated. At the restrictive temperature these display acute growth arrest with small cell size. Extragenic suppressor analysis identified Zip1, a bZIP transcription factor, as a target for Pof1. Zip1 is shown to be stabilised in pof1 mutants, Pof1 binds only phosphorylated forms of Zip1, and Zip1 is ubiquitylated in vivo, indicating that Zip1 is a substrate of SCFpof1. Genome-wide DNA microarray assay shows that many cadmium-induced genes are under the control of Zip1, suggesting Zip1 plays a role in the cadmium response. Consistently, zip1 mutants are hypersensitive to cadmium and unlike wild type, lose cell viability under this stress. Intriguingly, cadmium exposure results in upregulation of Zip1 levels and leads wild type cells to arrest growth with small cell size, reminiscent of pof1 phenotypes. Our results indicate that Zip1 mediates growth arrest in response to cadmium, which is essential to maintain viability. Normally growing cells prevent this response through constitutive ubiquitylation and degradation of Zip1 via SCFpof1.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available