RESEARCH SUMMARY

At present, with 1.7 million deaths each year, cancer represents the second most important cause of death in Europe. In up to 50% of all human cancers, constitutively enhanced expression of proto-oncogenes of the myc family is a characteristic signature.

Myc deregulation is due to rearrangements or other mutations in either one of the three myc genes. Myc proteins are members of a basic region/helix-loop-helix/leucine zipper (bHLHZip) transcription factor family (N-, L- and c-Myc) that can either activate or repress expression of their target genes.

The study of Myc function is a complex task. Myc members have been shown to bind to several thousand loci in the genome of humans and mice and regulate a variety of different genes. This large number of Myc targets affects a wide range of biological processes such as cell cycle control, apoptosis, protein synthesis, energetic metabolism, senescence, cell polarity and cell differentiation, which all are known to play a role in human cancer development. However, it remains to be determined which of these functions are the most relevant in Myc-dependent tumourigenesis. Among all these Myc functions, the role of c-Myc in cell differentiation is poorly understood.

In this context, our group is interested in understanding the molecular mechanisms that mediate the action of the proto-oncogene c-myc in cell differentiation. With this aim in mind, we have focused our efforts to address this question in a well-defined setting in vivo such us B lymphocyte differentiation. In recent years, we have developed several conditional mouse models to inactivate c-Myc at different developmental stages in B lymphocytes. These models have proved to be very useful to place c-Myc in the context of the transcription factors necessary for B lymphocyte differentiation. Finally, we expect to translate all this knowledge to pathological situations caused by deregulation of c-Myc expression in B lymphocytes.