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Title: Investigating the role of PTPN13 and ENTR1 in apoptotic cell death and proliferation
Author: Carmona Serrano, Antonio
ISNI:       0000 0004 7966 9806
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Death receptor Fas/CD95 is a crucial component in the regulation of ligand induced apoptosis in many cell types. It is well known that several cancers exhibit a decreased cell surface expression of Fas and consequently escape the control of Fas-mediated apoptosis, although underlying mechanisms are unclear. PTPN13, a multi-PDZ domain phosphatase, directly interacts with Fas and low surface levels of Fas have been previously correlated with increased levels of PTPN13 in a wide variety of tumour cell lines. Here we report that ENTR-1, an established interacting partner of PTPN13, also regulates cell surface levels of Fas. ENTR-1 forms a novel endocytic complex with PTPN13 that controls Fas-mediated apoptotic signaling by regulating the delivery of internalized Fas receptors from the early endosomes to the endolysosomal degradation pathway. The complex mediates the endosome-to-lysosome sorting of Fas via Dysbindin-Hrs1 axis thereby controlling termination of Fas signal transduction. Taken together, our data provide novel insights into the molecular mechanism of Fas post­endocytic trafficking and signaling. As downregulation of any component of the complex increases Fas receptor levels at the cell surface and affects the sensitivity of the cells to Fas-mediated apoptosis, our findings open possible explanations on how cancer cells regulate cell surface levels of death receptors.
Supervisor: Erdmann, Kai S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available