The starting point of the work described in tius thesis was a novel gene, CAN, that had been cloned by virtue of its involvement in translocation (6;9) (von Lindern, 1990), a recurrent chromosomal aberration defining a specific subtype of acute myeloid leukemia. Tills gene's predicted amino acid sequence showed no homology to known proteins (chapter 3), and therefore its cellular function was unknown. The protein encoded by CANIs fusion partner in the (6;9) translocation, DEK, also had no significant homology to proteins in the database. Consequently, the role of the chimeric DEK-CAN fusion protein in t(6;9)-associated leukemogenesis was a complete mystery. In addition, illl'itl'o studies to show the oncogenic function ofDEK-CAN consistently proved unsuccessful (M. von Lindem, J. Boer, G. Grosveld, unpublished results). To gain understanding of the possible function ofDEK-CAN, as well as the normal cellular functions ofDEK and CAN, we analyzed their primary amino acid stmctures (chapter 3 and 4), studied their subcellular localization (chapter 3), and looked for interacting proteins (chapter 5 and 6). In these studies, we focused on the CAN protein, since this protein had also been found in another leukemia-related fusion protein, SET-CAN (von Lindem, 1992), which suggests that it could playa more general role in leukemogenesis. In view of the difficulty reproducing the oncogenic effect of the DEK-CAN gene in vitro, and toxic effects caused by overexpression of DEK-CAN, we also set out to create an ill vivo system to mimic translocation (6;9) in transgenic mice using Cre-mediated recombination (chapter 8).

CAN protein, DNA, meyloid leukemia, molecular genetics
D. Bootsma (Dirk)
Erasmus University Rotterdam
Koningin Wilhelminafonds (KWF)
978-90-90-10093-7
hdl.handle.net/1765/17815
Erasmus MC: University Medical Center Rotterdam

Fornerod, M.W.J. (1997, January 8). The CAN Protein: A Mediator of Nuc1eocytoplasmic Transport with Oncogenic Properties. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/17815