Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus.
In infantile leukemias and therapy-related leukemias, the MLL gene is frequently found to be disrupted and fused to various translocation partner genes, such as AF4/FEL, LTG9/AF9 and LTG19/ENL as a result of 11q23 translocations. We previously showed that the N-terminal portion common to various chimeric MLL products, as well as to MLL-LTG9 and MLL-LTG19, localizes in the nuclei, and therefore suggested that it might play an important role in leukemogenesis. In the present study, MLL-AF6 chimeric products found in the t(6;11)(q27;q23) translocation were analysed since AF6, a Ras-binding protein, exhibits a different subcellular localization from that of LTG9/AF9 and LTG19/ENL. Immunofluorescence staining data and cell fractionation analyses demonstrated that MLL-AF6 chimeric products localize in the nuclei despite the fact that AF6 itself localizes in the cytoplasm, confirming the importance of the nuclear localization of chimeric MLL products. The region in the N-terminal portion of MLL responsible for this nuclear localization was examined and found to be a region containing AT-hook motifs.
Joh
T
T
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya, Japan.
Yamamoto
K
K
Kagami
Y
Y
Kakuda
H
H
Sato
T
T
Yamamoto
T
T
Takahashi
T
T
Ueda
R
R
Kaibuchi
K
K
Seto
M
M
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002451:Cell Compartmentation; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014162:Transfection; D014178:Translocation, Genetic; D018631:ras Proteins / Q000378:metabolism
C095516:AFDN protein, human; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D009218:Myosins; D016547:Kinesins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins