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Role of the Trib1 pseudokinase in breast cancer pathology

Year:
2015
Duration:
42 months
Approved budget:
$1,128,825.06
Researchers:
Dr Peter Mace
Health issue:
Cancer (oncology)
Proposal type:
Project
Lay summary
Inappropriately high expression of genes that regulate cell signalling is a hallmark of cancer. The TRIB1 gene lies in a region of DNA that is frequently amplified in breast cancer and also includes the MYC oncogene, which augments cancer signalling. The TRIB1 gene product is itself known to drive development of acute myeloid leukaemia, but its role in breast cancer has not been thoroughly characterised. We will determine three-dimensional structures that show how Trib1 protein binds to its substrates to drive acute myeloid leukaemia. This will establish a three-dimensional template for drugs that could disrupt these interactions for cancer therapy. We will also identify which Trib1 binding-partners are most relevant to breast cancer progression. This will pinpoint the signalling pathways that should be therapeutically targeted in breast cancer and the large proportion of other tumour types that overexpress Trib1.