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Title: Kinase activation and transformation by NUP214-ABL1 is dependent on the context of the nuclear pore
Authors: De Keersmaecker, Kim
Rocnik, Jennifer L
Bernad, Rafael
Lee, Benjamin H
Leeman, Dena
Gielen, Olga
Verachtert, Hanne
Folens, Cedric
Munck, Sebastian
Marynen, Peter
Fornerod, Maarten
Gilliland, D. Gary
Coois, Jan # ×
Issue Date: Jul-2008
Publisher: Cell press
Series Title: Molecular cell vol:31 issue:1 pages:134-142
Abstract: Genetic alterations causing constitutive tyrosine kinase activation are observed in a broad spectrum of cancers. Thus far, these mutant kinases have been localized to the plasma membrane or cytoplasm, where they engage proliferation and survival pathways. We report that the NUP214-ABL1 fusion is unique among these because of its requisite localization to the nuclear pore complex for its transforming potential. We show that NUP214-ABL1 displays attenuated transforming capacity as compared to BCR-ABL1 and that NUP214-ABL1 preferentially transforms T cells, which is in agreement with its unique occurrence in T cell acute lymphoblastic leukemia. Furthermore, NUP214-ABL1 differs from BCR-ABL1 in subcellular localization, initiation of kinase activity, and signaling and lacks phosphorylation on its activation loop. In addition to delineating an unusual mechanism for kinase activation, this study provides new insights into the spectrum of chromosomal translocations involving nucleoporins by indicating that the nuclear pore context itself may play a central role in transformation.
URI: 
ISSN: 1097-2765
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Laboratory of Molecular Biology of Leukemia
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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