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Title: Interaction studies on the transforming virus target tip-1
Author: Shalaby, Manal
ISNI:       0000 0004 2670 8234
Awarding Body: The University of Manchester
Current Institution: University of Manchester
Date of Award: 2009
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The class 1 PDZ domain Tip-1 protein was firstly identified as a binding partner for the Human T-Cell Leukaemia Virus type 1 (HTLVl) Tax oncoprotein. It was later also shown to interact with: the RhoA signalling effector rhotekin, the wnt signalling effector β-catenin and the E6 oncoprotein from high-risk HPV16 but not low risk HPV6. These observations suggested that Tip-1 may be an important "hub" protein that is involved in pathways with a proven link to carcinogenesis. Based on these finding, it was decided to further characterise the cellular role of Tip-1 by carrying out a yeast two-hybrid screen to identify new binding partners in order to uncover potentially novel functions of this protein. This identified an intracellular fragment of the transmembrane receptor Plexin Dl and a C-terminal fragment of the AT Hook DNA binding containing l(AHDCl) protein which also had a carboxyl terminal PDZ domain binding site consensus sequence. Both of these interactions were confirmed by yeast mating assay which was also used to show that mutant constructs of AHDCl lacking the carboxyl PDZ binding site did not bind Tip-L The Tip-1 protein was subsequently expressed in bacteria and purified as a glutathione transferase (GST) fusion product whilst full length AHDCl was cloned and expressed by in-vitro transcription / translation (IVTT).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available