Use this URL to cite or link to this record in EThOS:
Title: PAX6 protein-protein interactions
Author: Cooper, S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
The gene PAX6 is located on chromosome 11 (11p13) and encodes a transcription factor (PAX6) that is expressed early in development. The PAX6 protein is expressed in the developing eye, regions of the brain, central nervous system (CNS), nasal epithelium and pancreas. PAX6 is best known for its role eye development with heterozygous mutations causing congenital ocular malformations. However, it must be remembered that PAX6 has multiple functions in the brain including specification of neuronal subtypes and axon guidance. There is growing understanding of the role of PAX6 as a transcription factor during development, and many of its DNA targets have recently been defined. However, almost nothing is known about the proteins with which PAX6 interacts. In the initial stage of my research I identified a conserved region consisting of the final 32 amino acids of the PST (proline, serine and threonine rich) domain of PAX6. Based on sequence homology and secondary structure predictions I classed this region as a novel domain, the ‘C terminal domain’. Next I used the yeast 2-hybrid system to investigate possible PAX6 protein interactions. By screening a mouse brain cDNA library with the C terminal domain and whole PST domain, I identified three novel and interesting interactors, HOMER3, DNCL1 and TRIM11. I re-confirmed these interactions in a pairwise manner using the yeast 2-hybrid system, and I showed that the C terminal domain was vital for the interactions between PAX6 and HOMER3 or DNCL1. Furthermore, certain C terminal mutations that are known to cause ocular malformations in patients are also sufficient to reduce or abolish these interactions. I attempted to further characterise the interactions by co-immunoprecipitation. However, this was not possible due to technical difficulties.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available