The expression of Tumor protein D52 (TPD52) family members is deregulated in many types of cancer. When overexpressed, it is suggested that they increase cell proliferation and migration/invasion as well as avoid apoptosis. Deregulation in the expression of the TPDs is therefore linked to poor prognosis. Little characterisation has been carried out to date, but it is known that the TPDs are found in association with components of the membrane trafficking pathway. The aim of this work is to uncover how the least studied member of the family, TPD54, affects cellular processes involved in carcinogenesis, such as cell migration and invasion. By using the knocksideways method, we have been able to map the cellular localisation of TPD54 and have identified association partners. These associations have been confirmed by immunoprecipitation and mass spectrometry analysis. Amongst these was the small GTPase Rab14. We have also found that TPD54 is involved in the trafficking of receptors containing a dileucine motif in their cytosolic tail, but not a tyrosine-based or NPXY motif. With the mapping of the localisation of TPD54, we hypothesise that TPD54 is on the recycling route following the Golgi apparatus, and in association with Rab14, regulates the trafficking of receptors containing a dileucine motif. Integrins are receptors controlling cell migration. They can be trafficked through the Golgi apparatus before being recycled back to the plasma membrane. This recycling route is not well characterised. We therefore hypothesise that TPD54 regulates this route with Rab14, and that this is the reason why TPD54 is important for cell migration, and that a defect in its function can cause cancer.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:752474 |
| Date | January 2017 |
| Creators | Larocque, Gabrielle |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/107000/ |
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