Functional consequences of threonine-60 phosphorylation of pituitary-tumor transforming gene and The role of vascular endothelial growth factor in decidualisation

Foster, Jessica (2013). Functional consequences of threonine-60 phosphorylation of pituitary-tumor transforming gene and The role of vascular endothelial growth factor in decidualisation. University of Birmingham. M.Res.

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Abstract

Pituitary-tumour transforming gene (PTTG) is an integral part of the spindle assembly checkpoint. Recently, a Threonine-60 (T60) mutation in PTTG has been found to induce chromosomal instability and invasiveness. We hypothesise phosphorylation at the T60 residue modulates PTTG degradation in mitosis. We aimed to investigate this using mutant T60 PTTG forms, examining the interaction between the anaphase promoting complex/cyclosome (APC/C) co-activator Cdc20, and the ubiquitylation potential of these proteins. Results indicate that mutation of the T60 site does not abrogate ubiquitination by the APC/C and increases binding to Cdc20 compared to that of wild-type PTTG.

Vascular endothelial growth factor (VEGF) is a fundamental part of the decidualisation process and implantation preparation. Its role in vascular reorganisation has long been established, however its function in stromal cells remains to be seen. This study hypothesises that VEGF is expressed upon decidualisation of stromal cells, potentially through activation of cAMP and FOXO1. We aimed to decidualise the immortal stromal cell line St-T1b through progesterone and cAMP stimulation, examine VEGF expression in decidualisation, and investigate potential VEGF gene regulation. Results suggest VEGF expression increases upon decidualisation in a manner related to FOXO1 expression, and that VEGF expression by decidual cells has potential function implications.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):