SKP2-mediated ubiquitination and cancer

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/145656

Funding Status
Closed

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Funded Activity Summary

The future of cancer therapy lies in the tailoring of treatment to the characteristic of individual tumour. We have previously identified a subset of breast tumours that are characterised by the presence of large excess of proteins called D-type cyclins. Similar overexpression of cyclin D1 has been shown to lead to the development of cancer in mammary gland in animal models. In normal cells, D-type cyclins are degraded rapidly, therefore the regulation of protein degradation, or proteolysis, is crucial in preventing the accumulation of D-type cyclins. In the subset of breast cancers we have identified, D-type cyclin proteolysis is defective. We, and others, have obtained evidence for the involvement of the SKP2 gene in the proteolysis of D-type cyclins. SKP2 has also been shown to be required for the proteolysis of another important protein, called p27. In the clinic, accumulation of p27 in tumours is used as a good prognostic indicator. However, some exceptions have been found where the accumulation of p27 correlates with aggressive tumours. As D-type cyclins are able to counteract the effect of p27, we hypothesise that the aggressive behaviour of these tumours is due to the simultaneous accumulation of D-type cyclins and that this is due to a mutation in the SKP2 gene. The experiments described in this proposal are designed to test this hypothesis. As the choice of treatment is affected by the interpretation of p27 levels, the results obtained from this study may have a direct impact in the clinic.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $227,036.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Oncology And Carcinogenesis

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Breast cancer | CDK inhibitor | Cancer | D-type cyclins | F-box proteins | Rb pathway | Womens health | ubiquitin-mediated proteolysis

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