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Regulation of transcriptional activators by the rb and mdm2 oncoproteins


The oncoprotein MDM2 and the tumour suppressor RB are important regulators of transcription factors (TFs): MDM2, for instance, inhibits the activity of p53, a TF that induces growth arrest or apoptosis upon DNA-damage, whereas RB inhibits - amongst others - the activity of E2F, a TF that promotes cell division. A precise control of these processes is a prerequisite for a reliable cell division with an intact genome. We found that MDM2 stimulates E2F and that RB interacts with p53. Therefore, it shall be investigated how MDM2 and RB regulate p53 and E2F, TFs with acidic activation domains, and how this affects cellular processes like growth control and apoptosis. Since we found that MDM2 can also interact with and activate the TF AP1, but not SP1, a TF with a glutamine rich activation domain, it shall be investigated, whether MDM2 is a general adaptor molecule of transcription.
Finally, a library screen using the yeast two hybrid system shall be carried out to identify further molecules interacting with and regulating the activation domain of E2F1.
The findings of this project should contribute to the understanding of the nature of cancer and to developing new drugs for treatment of various types of this disease.

Funding Scheme

RGI - Research grants (individual fellowships)
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University of Cambridge
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CB2 1QR Cambridge
United Kingdom

Participants (1)

Not available