Aberrant intracellular localization of SET-CAN fusion protein, associated with a leukemia, disorganizes nuclear export.
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-Ibeta, 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-Ibeta-CAN/Nup214, we have examined its subcellular localization. Immunofluorescence analyses showed that SET/TAF-Ibeta and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF-Ibeta-CAN/Nup214 is localized in the nucleus. SET/TAF-Ibeta-CAN/Nup214 interacted with hCRM1, one of the nuclear export factors, and caused aberrant intracellular localization of hCRM1. In cells expressing SET/TAF-Ibeta-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-Ibeta-CAN/Nup214 may be involved in oncogenesis.
Saito
Shoko
S
Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Miyaji-Yamaguchi
Mary
M
Nagata
Kyosuke
K
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000503:physiopathology*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010957:Plasmids; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015514:Oncogene Proteins, Fusion; C481746:SET-CAN fusion protein, human