Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.654881
Title: The role of Sin1 in cell survival
Author: Paramo Sanchez, Blanca Estela
ISNI:       0000 0004 5360 9813
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2015
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Cancer and neurodegeneration are detrimental conditions associated with an inappropriate regulation of cell survival and cell death, causing compromised cells to evade death or excessive death of healthy neurons. The mammalian target of rapamycin complex 2 (mTORC2) has been implicated in the regulation of cell survival by phosphorylating the protein kinase Akt. This is dependent upon the scaffold protein Sin1, a core component of mTORC2. The requirement of Sin1 in cell survival, and in particular in neuronal survival, has not been established due to the early embryonic lethality of mice with a targeted deletion of the Sin1 gene. To circumvent this issue, a novel conditional mouse knockout model was established. The role of Sin1 in regulating cell survival was evaluated in fibroblasts and cortical neurons. The loss of Sin1 significantly affected the phosphorylation and activity of Akt in fibroblasts and caused a reduction in cell survival by potentially inducing premature senescence. In contrast, the loss of Sin1 caused an increase in caspase-independent cell death in cortical neurons. Gene-expression analysis of Sin1 knockout cortical neurons demonstrated an important down-regulation of transcription factors, cytoskeletal proteins and components of signalling pathways involved in neuronal survival, aiding to uncover the mechanism by which Sin1 promotes neuronal survival. Taken together, the results presented in this study show a key role of the scaffold protein Sin1 in regulating neuronal survival.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.654881  DOI: Not available
Keywords: survival ; apoptosis ; necroptosis ; mTORC2 Akt ; neuronal survival
Share: