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

Mai Suzuki, Kazutsune Yamagata, Mika Shino, Yukiko Aikawa, Koichi Akashi, Toshio Watanabe, Issay Kitabayashi

研究成果: Contribution to journalArticle査読

6 被引用数 (Scopus)

抄録

The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies. Certain HOXA cluster genes and MEIS1 genes are upregulated in patients and mouse models that express CALM-AF10. 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. To investigate the influence of localization on leukemogenesis involving CALM-AF10, we determined the nuclear export signal (NES) within CALM that is necessary and sufficient for cytoplasmic localization of CALM-AF10. Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models. Furthermore, a fusion of AF10 with the minimal NES can immortalize bone-marrow cells and induce leukemia in mice. These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

本文言語英語
ページ(範囲)315-323
ページ数9
ジャーナルCancer Science
105
3
DOI
出版ステータス出版済み - 3 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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