WORFOLK, JACK,CHRISTOPHER,PETER (2018) Proteomic analysis of redox-dependent AGR2 complexes reveals a novel mucin quality control system in oesophageal adenocarcinoma. Masters thesis, Durham University.
|PDF (Proteomic analysis of redox-dependent AGR2 complexes reveals a novel mucin quality control system in oesophageal adenocarcinoma) - Accepted Version|
Disulphide bonds covalently linking cysteine residues, intramolecularly or intermolecularly, are often essential in ensuring the stability of secreted and cell surface proteins as well as facilitating correct spatial positioning of protein active sites. The protein disulphide isomerase (PDI) family of proteins catalyse the oxidation, reduction and isomerisation of these disulphide bonds. PDI proteins are vital for protein quality control and most are found ubiquitously. Anterior gradient-2 (AGR2) is an unusual tissue-restricted member of the PDI family that has gained considerable attention in the last 15 years because of its overexpression in a variety of different cancer types, including oesophageal adenocarcinoma. In this thesis it has been demonstrated that the OE19 late stage oesophageal adenocarcinoma cell line strongly expresses AGR2, and that in this cell line AGR2 can form redox-inducible, disulphide bond dependent complexes. It has also been shown, through the development and use of a novel, unbiased trapping and immunoprecipitation approach, that these AGR2 interacting proteins can be identified and compared. This approach has identified mucin isoforms that AGR2 preferentially binds as its primary clients and has revealed a host of ER chaperones involved in this quality control complex. This thesis lays the groundwork for the elucidation and definition of an AGR2-mucin quality control system within oesophageal adenocarcinoma and provides biomarkers and potential therapeutic targets for identification and treatment of AGR2-positive cancers.
|Item Type:||Thesis (Masters)|
|Award:||Master of Science|
|Faculty and Department:||Faculty of Science > Biological and Biomedical Sciences, School of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||17 Jan 2019 14:23|