Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus

Tatsuroh Joh, Kazuhito Yamamoto, Yoshitoyo Kagami, Harumi Kakuda, Takeyuki Sato, Takaharu Yamamoto, Toshitada Takahashi, Ryuzo Ueda, Kozo Kaibuchi, Masao Seto

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Abstract

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.

Original languageEnglish
Pages (from-to)1681-1687
Number of pages7
JournalOncogene
Volume15
Issue number14
DOIs
Publication statusPublished - 01-01-1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Joh, T., Yamamoto, K., Kagami, Y., Kakuda, H., Sato, T., Yamamoto, T., Takahashi, T., Ueda, R., Kaibuchi, K., & Seto, M. (1997). Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus. Oncogene, 15(14), 1681-1687. https://doi.org/10.1038/sj.onc.1201332