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Biological role of the atf2 transcription factor. Molecular mechanisms involved in atf2 regulated transcriptional activation


Research objectives and content
Our research project will focus on two major points concerning the activity of the ATF2 transcription factor; 1) How does ATF2 activate transcription?, and 2) Biological role of ATF2. I) Previous work in Nic Jones' laboratory failed to detect any direct interaction between the activation domain of ATF2 and components of the basic transcription machinery. One of our major goals is to identify proteins that interact with the N-terminus of ATF2, preferably in a phosphorylation dependent manner. We will also assay if ATF2 can activate transcription by itself in an in vitro transcription system using chromatin templates. 2) To study the role of ATF2, three different dominant negative versions of the protein have been produced in Nic Jones' laboratory. Preliminary results from this lab suggest that these negative versions block T cell development. We will test why T cell development is blocked, by using retroviruses mediated gene transfer on fetal thymus organ culture. The same approach could be used to examine the involvement of ATF2 in the induction of apoptosis. Training content (objective, benefit and expected impact)
The use of dominant negative versions of ATF2 will prevent the expected redundancy between ATF2 and ATFa, and will avoid potential problems to study genes controlling particular biological programs in knockout mice (long-term procedures and possibility of embryonic lethality). Links with industry / industrial relevance (22)

Call for proposal

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Imperial Cancer Research Fund
44,lincoln's inn fields
CM13 1LX London
United Kingdom

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EU contribution
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Participants (1)