Objective Sequential activation of different oncogenes drive the step-wise progression of precancerous cells to highly malignant tumors. A molecular understanding of the transformation events is crucial to develop anti-cancer therapies. In this sense, The AP-1 transcription factor has gained special attention in the last decades due to its key role in the tumor development. AP-1 comprises a family of dimeric basic region-leucine zipper transcription factors. The founding members of the AP-1 family, c-Fos and c-Jun, were both originally identified as oncogenes. C-Jun is the most potent transcriptional activator in its group. The induction of AP-1 by pro-inflammatory cytokines and genotoxic stress is mostly mediated by JNK that mediates c-Jun N-terminal phosphorylation in its transactivation domain, increasing the transcription of target genes. The B-cell Leukemia-6 (BCL6) proto-oncogene encodes a transcriptional repressor required for the formation of Germinal Centers (GC) which are important in pathology, since GC B cells are thought to represent the cell of origin of most types of human B cell lymphomas. Transgenic mouse overexpressing BCL6 have been generated and they could not fully recapitulate the human disease, suggesting that cooperation with a second oncogene may be required. Previously it has been observed that c-Jun and Bcl6 physically interact, however the significance of this interaction for tumour development was not investigated. The host lab has recently confirmed the association of c-Jun and BCL6 and in this proposal we will investigate whether c-Jun activation cooperates with BCL6 in lymphoma development. A multidisciplinary study, including in vitro and in vivo approaches will be used to define the nature of the cooperation between BCL6 and c-Jun in lymphoma development and progression. Transgenic approaches, including generation of a lymphoma mouse model together with biochemistry and molecular biology techniques will be used to unravel their cooperation Fields of science natural sciencesbiological sciencesbiochemistrymedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesmolecular biology Keywords AP-1 BCL6 Health sciences c-Jun leukemia lymphoma mice oncogenic hits therapy Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2007-2-1-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator CANCER RESEARCH UK LBG EU contribution € 178 307,05 Address 2 Redman Place E20 1JQ LONDON United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Administrative Contact Jacobs Louisa (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
