|Title:||Characterisation of APC localisation, dynamics and functions at the centrosome|
|Authors:||Lui, Christina Ka-Wing|
|Keywords:||APC, centrosome, localisation, microtubule, nucleation, dynamics|
|Publisher:||Uniersity of Sydney.|
Faculty of Medicine.
Western Clinical School.
|Abstract:||Adenomatous polyposis coli (APC) is a tumour suppressor protein and regulator of the wnt signalling pathway. APC is mutated in >90% of colorectal tumours and these mutations often translate a shorter truncated protein. Truncated APC has now been linked to mitotic spindle dysfunction. Mitotic spindles are nucleated from centrosomes and in cells expressing cancer mutant forms of APC cause aberrant spindle attachments leading to an increased rate of chromosome instability. Both full-length and mutant APC persistently localise to the centrosome throughout the cell cycle, however its role at interphase centrosomes are ill-defined. In this thesis, using a combination of immunofluorescence microscopy, retention assays and fluorescence recovery after photobleaching (FRAP) techniques, both wild-type and mutant forms of APC were found to be highly dynamic at the interphase centrosome, but highly retained at the mitotic centrosome, and targeted by the Armadillo domain of APC. Using various centrosome functional assays, APC was found to contribute to microtubule nucleation, but was not involved in centrosome amplification or separation. Using protein interaction methods, several novel APC binding partners ranging from protein regulators of the centrosome to microtubule-associated proteins were also discovered.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
|LUI Christina - Final Thesis.pdf||Final Thesis||17.79 MB||Adobe PDF|
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