TY - JOUR
T1 - Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus
AU - Joh, Tatsuroh
AU - Yamamoto, Kazuhito
AU - Kagami, Yoshitoyo
AU - Kakuda, Harumi
AU - Sato, Takeyuki
AU - Yamamoto, Takaharu
AU - Takahashi, Toshitada
AU - Ueda, Ryuzo
AU - Kaibuchi, Kozo
AU - Seto, Masao
N1 - Funding Information:
We would like to thank Drs T Miki, S Nakazawa and R Ishida for their valuable discussions and Dr H Teraoka for the gift of purified DNA-activated protein kinase (p470) protein. We greatly appreciate the technical assistance of Ms H Suzuki and M Sugiyama. This work was supported in part by a Grant-in-aid for the Second-Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, a Grant-in-aid for Science in Primary Areas (Cancer Research), a Grant-in-aid for the Encouragement of Young Scientists from the Ministry of Education, Science and Culture, Japan, a Grant-in-Aid from The Japanese Foundation for Multidisciplinary Treatment of Cancer and the Bristol-Myers Squibb Unrestricted Biomedical Research Grants Program.
PY - 1997
Y1 - 1997
N2 - 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 LTGI9/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.
AB - 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 LTGI9/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.
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U2 - 10.1038/sj.onc.1201332
DO - 10.1038/sj.onc.1201332
M3 - Article
C2 - 9349501
AN - SCOPUS:9844268506
SN - 0950-9232
VL - 15
SP - 1681
EP - 1687
JO - Oncogene
JF - Oncogene
IS - 14
ER -