Subcellular localization of the MEN, MLL/MEN and truncated MLL proteins expressed in leukemic cells carrying the t(11;19)(q23;p13.1) translocation.
The t(11;19)(q23;p13.1) translocation is exclusively associated with myeloid leukemias. Previously, we cloned several species of MLL/MEN chimeric cDNAs in a patient with myeloid leukemia carrying the t(11;19)(q23;p13.1) translocation. The MEN sequence directly followed the 5' region of MLL cDNA in some species and otherwise there presented an inserted sequence of 120 bp between the MLL and MEN sequences in others. Because the insertion sequence contained an in-frame termination codon, they coded only for the NH2-terminal part of MLL (truncated MLL). We also cloned the normal MEN cDNA in full-length with a cDNA library derived from K562 cells. We expressed the normal MEN, MLL/MEN chimeric and truncated MLL proteins in COS7 cells with the corresponding cDNAs and detected them with antibodies raised against the MEN and MLL peptides. Immunostaining and subcellular fractionation showed nuclear localization of all these proteins. These findings suggested that MLL/MEN chimeric cDNAs were actually translated into both MLL/MEN fusion and truncated MLL proteins and that they were localized in the nucleus of leukemic cells. Recently, Conaway et al. reported that MEN is an RNA polymerase II elongation factor. The leukemogenesis by the t(11;19)(q23;p13.1) translocation may have resulted from the alteration of transcription regulation induced by the MLL/MEN fusion protein and/or the truncated MLL protein.
Kanda
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Mitani
K
K
Tanaka
T
T
Tanaka
K
K
Ogawa
S
S
Yazaki
Y
Y
Hirai
H
H
D000818:Animals; D019556:COS Cells; D002471:Cell Transformation, Neoplastic; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics* / Q000648:ultrastructure; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein; D010445:Peptide Elongation Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics*; D013347:Subcellular Fractions / Q000737:chemistry*; D014157:Transcription Factors; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D010445:Peptide Elongation Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase