Objective
The Id (Inhibitor of differentiation) family consists of four related transcription factors that are expressed at high levels in rapidly proliferating cells, including those found tumour cells. Overexpression of Id proteins in transgenic mice causes cancers. Ids have been shown to inhibit differentiation and promote cell proliferation in a variety of systems. This is achieved through interactions with other transcription factors such as MyoD, E47 and Ets. To date, all of the published targets of Id regulation are genes encoding protein. However we have discovered that Ids can also stimulate expression of short non-coding RNAs that are transcribed by RNA polymerase (pol) III, such as tRNA and 5S rRNA. This regulation appears to be direct, as endogenous Id proteins can be crosslinked in vivo to pol III transcribed genes. We also detect E47, a protein that promotes differentiation of several cell types, at these genes and find that it represses pol III transcription. This is consistent with the established antagonism between Id proteins and E47. It is well documented that pol III transcripts are overexpressed in many tumours. Our data suggests that, direct activation by Id proteins may contribute to this. It may be important, because elevated tRNA expression was recently shown to have proliferative and oncogenic effects in cell culture and in mice.
This proposal aims to dissect molecular mechanisms responsible for Id mediated activation of tRNA and other pol III transcribed genes. We will also investigate the functional significance of pol III-Id interaction. RNAi will be used to test the hypothesis that Id proteins stimulate and E47 antagonises the proliferative and transforming effects of tRNA synthesis by pol III. Furthermore we will test if raising pol III transcription is required for the oncogenicity of an Id. Such experiments elucidate activity of Id proteins and their association with cancer.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
4051 Basel
Switzerland
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