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Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.

Suzuki M, Yamagata K, Shino M, Aikawa Y, Akashi K, Watanabe T, Kitabayashi I - Cancer Sci. (2014)

Bottom Line: The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies.Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia.These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.

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Dot1L mainly localize in the nucleus in CALM-AF10-induced or NES2-AF10-induced leukemic cells. (a) Subcellular distribution of endogenous Dot1L in CALM-AF10-induced or NES2-AF10-induced leukemic cells. Cytospins of the cells were stained with anti-FLAG antibody (red), anti-DOT1L antibody (green) and DAPI (blue) and observed by confocal laser scanning microscopy. Note that GFP expression was not detected in the condition. (b) Subcellular distribution of endogenous Dot1L in the control vector-infected murine using fluorescence microscopy. (c) Population of leukemia cells expressing DOT1L and CALM-AF10 or FLAG-NES2-AF10 in the nucleus and the cytoplasm shown in (a) and (b). The scale bar represents 5 μm in (a) and 10 μm in (b).
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fig05: Dot1L mainly localize in the nucleus in CALM-AF10-induced or NES2-AF10-induced leukemic cells. (a) Subcellular distribution of endogenous Dot1L in CALM-AF10-induced or NES2-AF10-induced leukemic cells. Cytospins of the cells were stained with anti-FLAG antibody (red), anti-DOT1L antibody (green) and DAPI (blue) and observed by confocal laser scanning microscopy. Note that GFP expression was not detected in the condition. (b) Subcellular distribution of endogenous Dot1L in the control vector-infected murine using fluorescence microscopy. (c) Population of leukemia cells expressing DOT1L and CALM-AF10 or FLAG-NES2-AF10 in the nucleus and the cytoplasm shown in (a) and (b). The scale bar represents 5 μm in (a) and 10 μm in (b).

Mentions: It has been reported that CALM-AF10 interacts with the histone methyltransferase DOT1L to mediate H3K79 hypermethylation at the Hoxa5 locus.9 To determine whether Dot1L colocalizes with CALM-AF10 and NES2-AF10 in the leukemia cells, we performed immunofluorescence analysis. Dot1L mainly localized in the nucleus while CALM-AF10 and NES2-AF10 mainly localized in the cytoplasm (Fig.5a,b). Dot1L partially colocalized with both CALM-AF10 and NES2-AF10, but neither CALM-AF10 nor NES2-AF10 altered the localization of Dot1L (Fig.5a).


Nuclear export signal within CALM is necessary for CALM-AF10-induced leukemia.

Suzuki M, Yamagata K, Shino M, Aikawa Y, Akashi K, Watanabe T, Kitabayashi I - Cancer Sci. (2014)

Dot1L mainly localize in the nucleus in CALM-AF10-induced or NES2-AF10-induced leukemic cells. (a) Subcellular distribution of endogenous Dot1L in CALM-AF10-induced or NES2-AF10-induced leukemic cells. Cytospins of the cells were stained with anti-FLAG antibody (red), anti-DOT1L antibody (green) and DAPI (blue) and observed by confocal laser scanning microscopy. Note that GFP expression was not detected in the condition. (b) Subcellular distribution of endogenous Dot1L in the control vector-infected murine using fluorescence microscopy. (c) Population of leukemia cells expressing DOT1L and CALM-AF10 or FLAG-NES2-AF10 in the nucleus and the cytoplasm shown in (a) and (b). The scale bar represents 5 μm in (a) and 10 μm in (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317939&req=5

fig05: Dot1L mainly localize in the nucleus in CALM-AF10-induced or NES2-AF10-induced leukemic cells. (a) Subcellular distribution of endogenous Dot1L in CALM-AF10-induced or NES2-AF10-induced leukemic cells. Cytospins of the cells were stained with anti-FLAG antibody (red), anti-DOT1L antibody (green) and DAPI (blue) and observed by confocal laser scanning microscopy. Note that GFP expression was not detected in the condition. (b) Subcellular distribution of endogenous Dot1L in the control vector-infected murine using fluorescence microscopy. (c) Population of leukemia cells expressing DOT1L and CALM-AF10 or FLAG-NES2-AF10 in the nucleus and the cytoplasm shown in (a) and (b). The scale bar represents 5 μm in (a) and 10 μm in (b).
Mentions: It has been reported that CALM-AF10 interacts with the histone methyltransferase DOT1L to mediate H3K79 hypermethylation at the Hoxa5 locus.9 To determine whether Dot1L colocalizes with CALM-AF10 and NES2-AF10 in the leukemia cells, we performed immunofluorescence analysis. Dot1L mainly localized in the nucleus while CALM-AF10 and NES2-AF10 mainly localized in the cytoplasm (Fig.5a,b). Dot1L partially colocalized with both CALM-AF10 and NES2-AF10, but neither CALM-AF10 nor NES2-AF10 altered the localization of Dot1L (Fig.5a).

Bottom Line: The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies.Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia.These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus