Kinase Activation and Transformation by NUP214-ABL1 Is Dependent on the Context of the Nuclear Pore

Kim De Keersmaecker, Jennifer L. Rocnik, Rafael Bernad, Benjamin H. Lee, Dena Leeman, Olga Gielen, Hanne Verachtert, Cedric Folens, Sebastian Munck, Peter Marynen, Maarten Fornerod*, D. Gary Gilliland, Jan Cools*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)134-142
Number of pages9
JournalMolecular Cell
Volume31
Issue number1
DOIs
Publication statusPublished - 11 Jul 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'Kinase Activation and Transformation by NUP214-ABL1 Is Dependent on the Context of the Nuclear Pore'. Together they form a unique fingerprint.

Cite this