Nuclear Export Signal Within CALM is Necessary for CALM-AF10-induced Leukemia

Overview

Journal Cancer Sci

Specialty Oncology

Date 2014 Jan 9

PMID 24397609

Citations 6

Authors

Mai Suzuki

Kazutsune Yamagata

Mika Shino

Yukiko Aikawa

Koichi Akashi

Toshio Watanabe

Issay Kitabayashi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins.

Komata Y, Kanai A, Maeda T, Inaba T, Yokoyama A Nat Commun. 2023; 14(1):1979.

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Prognostic relevance of genetic variations in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma.

Yu H, Du Y, Xu J, Zhang M Transl Cancer Res. 2022; 8(6):2485-2495.

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The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations.

Klein B, Deshpande A, Cox K, Xuan F, Zandian M, Barbosa K Nat Commun. 2021; 12(1):4130.

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A Novel Sequence in AP180 and CALM Promotes Efficient Clathrin Binding and Assembly.

Moshkanbaryans L, Xue J, Wark J, Robinson P, Graham M PLoS One. 2016; 11(8):e0162050.

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The ∼ 16 kDa C-terminal sequence of clathrin assembly protein AP180 is essential for efficient clathrin binding.

Chan L, Moshkanbaryans L, Xue J, Graham M PLoS One. 2014; 9(10):e110557.

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