Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export

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Abstract
The SET‐CAN fusion gene is the product of a chromosomal rearrangement found on 9q34 associated with an acute undifferentiated leukemia. SET‐CAN encodes an almost complete SET protein fused to the C‐terminal two‐thirds of CAN. SET is also known as TAF‐Iβ, a histone chaperone and intracellular inhibitor of protein phosphatase 2A, whereas CAN is identical to Nup214, a nucleoporin protein. To obtain insight into the leukemogenic function of SET/TAF‐Iβ‐CAN/Nup214, we have examined its subcellular localization. Immunofluorescence analyses showed that SET/TAF‐Iβ and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF‐Iβ‐CAN/Nup214 is localized in the nucleus. SET/TAF‐Iβ‐CAN/Nup214 interacted with hCRM1, one of the nuclear export factors, and caused aberrant intracellular localization of hCRM1. In cells expressing SET/TAF‐Iβ‐CAN/Nup214, a protein containing a nuclear export signal accumulated in the nucleus. The export of this protein was partially restored by overexpression of hCRM1. These results suggest that aberrantly localized molecules associated with SET/TAF‐Iβ‐CAN/Nup214 may be involved in oncogenesis.