Functional characterization of the nucleoporin CAN and CAN-derived leukemia-specific fusion proteins
Year: 1997
Type: dissertation
Abstract: Chromosome translocations are cytogenetically visible genetic abnormalities that are\noften associated with specific tumors. Characterization of the genes at the chromosome\nbreakpoints can give insights into the processes that transform normal cells to tumor\ncells. The (6;9) translocation, associated with acute myeloid leukemia and\nmyelodysplastic syndrome, fuses the DEK gene to CAN and results in the expression\nof a chimeric DEK-CAN gene. In a second chromosome rearrangement, found in one\npatient with acute undifferentiated leukemia, CAN is fused to SET. Knowledge of the\nnormal functions of the proteins encoded by the fusion partners is indispensable in\nunderstanding the mechanisms by which DEK-CAN and SET-CAN contribute to\nleukemogenesis. The aim of the research described here is to define the functions of\nCAN, which was identified as a nuclear pore complex component (nucleoporin), and of\nthe CAN-derived fusion proteins.\nThis thesis starts out with an introduction about chromosome aberrations in\nhematopoietic malignancies, that result in the generation of fusion genes. The DEK,\nSET, and CAN proteins are introduced, and a number of molecular mechanisms in\noncogenic transformation by fusion proteins are highlighted with examples (Chapter 1).\nThe chapters that follow describe our experimental work concerning the functions of\nCAN and DEK-CAN. First, we studied the consequences of loss of CAN function after\ndisruption of the mouse CAN gene by homologous recombination (Chapter 2). Second,\nthe effects of CAN and DEK-CAN expression on the growth, differentiation and survival\nof myeloid precursor cells were investigated (Chapter 3). Th
Author: Judith M. Boer
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2137698222