Analysis Of APC And APC Protein Complexes In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$110,786.00
Summary
Colorectal cancer is one of the foremost causes of death in Australia. A defective form of a protein called APC has been shown to be present in more than 80% of colon tumours. How APC contributes to colon cancer is still not known. We aim to determine the function of the APC protein by studying the APC protein and proteins that interact with APC in normal and cancerous colon epithelial cells. We will use cells derived from normal colon epithelium as well as from colon carcinomas. Once we have id ....Colorectal cancer is one of the foremost causes of death in Australia. A defective form of a protein called APC has been shown to be present in more than 80% of colon tumours. How APC contributes to colon cancer is still not known. We aim to determine the function of the APC protein by studying the APC protein and proteins that interact with APC in normal and cancerous colon epithelial cells. We will use cells derived from normal colon epithelium as well as from colon carcinomas. Once we have identified proteins that interact with APC in normal colonic cells, we will have a more complete understanding of the function of APC and its role in the development of colonic tumours.Read moreRead less
Functional Characterisation Of N4WBP5 And N4WBP5A, Novel Nedd4-interacting Proteins
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
The proteins that make up a cell must be correctly localised in order to perform their normal function. Specialised cellular activities are carried out in distinct compartments within a cell and proteins must correctly localise in them and traffic between them. Intracellular protein trafficking is a highly regulated process involving many components. Recent findings have shown that intracellular trafficking is regulated in many cases by distinct protein modifications. One such modification is ta ....The proteins that make up a cell must be correctly localised in order to perform their normal function. Specialised cellular activities are carried out in distinct compartments within a cell and proteins must correctly localise in them and traffic between them. Intracellular protein trafficking is a highly regulated process involving many components. Recent findings have shown that intracellular trafficking is regulated in many cases by distinct protein modifications. One such modification is tagging of a small protein called ubiquitin to proteins that are being trafficked. A focus of research in our laboratory is the study of a protein, called Nedd4, which directly tags proteins with ubiquitin. We have recently identified two novel proteins that interact with Nedd4 and localise to distinct subcellular compartments that are sites for the correct sorting and delivery of proteins trafficking within the cell. The main aim of our proposal is to characterise how these proteins function. We propose that these proteins are involved in intracellular trafficking and that they may function by targeting Nedd4 to the cellular trafficking machinery. This may be required for Nedd4 to tag molecules with ubiquitin that are involved in intracellular trafficking. Our experiments will test the functional relationship between Nedd4 and the novel proteins and determine the particular trafficking pathways in which these proteins are involved. Defects in cellular processes regulated by Nedd4 and other similar proteins cause a number of human diseases including an inherited form of hypertension and a specific group of cancers. In addition, a large number of human diseases result directly from defects which disrupt intracellular trafficking pathways. The results of this study will provide further insight into this essential cellular process and may ultimately contribute to the development of therapies for diseases resulting from defects in intracellular trafficking.Read moreRead less
Targeting Of The APC Tumour Suppressor To Mitochondria: Implications For APC Regulation And Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$390,116.00
Summary
Inherited mutations in the APC gene cause colon cancer, and kills 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by the age of 75. APC mutations change cells in different ways, triggering the cancer process. We have discovered a new pathway, involving altered movement of APC to mitochondria in tumour cells. This study will investigate how this cancerous change may help our understanding of colon cancer progression.