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Myeloid Leukemia Factor 1 inhibits erythropoietin-induced differentiation, cell cycle exit and p27Kip1 accumulation

Oncogene volume 23, pages 5105–5109 (2004)Cite this article

Abstract

Myeloid leukemia factor 1 (MLF1) is a novel oncoprotein involved in translocations associated with acute myeloid leukemia (AML), especially erythroleukemias. In this study, we demonstrate that ectopic expression of Mlf1 prevented J2E erythroleukemic cells from undergoing biological and morphological maturation in response to erythropoietin (Epo). We show that Mlf1 inhibited Epo-induced cell cycle exit and suppressed a rise in the cell cycle inhibitor p27Kip1. Unlike differentiating J2E cells, Mlf1-expressing cells did not downregulate Cul1 and Skp2, components of the ubiquitin E3 ligase complex SCFSkp2 involved in the proteasomal degradation of p27Kip1. In contrast, Mlf1 did not interfere with increases in p27Kip1 and terminal differentiation initiated by thyroid hormone withdrawal from erythroid cells, or cytokine-stimulated maturation of myeloid cells. These data demonstrate that Mlf1 interferes with an Epo-responsive pathway involving p27Kip1 accumulation, which inhibits cell cycle arrest essential for erythroid terminal differentiation.

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Acknowledgements

LW was a recipient of the Richard Walter Gibbon Fellowship. This work was supported by The National Health and Medical Research Council (254668), The Cancer Foundation of Western Australia and The Medical Research Foundation of Royal Perth Hospital.

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Authors and Affiliations

  1. Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Perth, 6000, WA, Australia

    Louise Natalie Winteringham, Simon Kobelke, James Howard Williams, Evan Ingley & Svend Peter Klinken

  2. Centre for Medical Research, The University of Western Australia, Perth, 6000, WA, Australia

    Louise Natalie Winteringham, Simon Kobelke, James Howard Williams, Evan Ingley & Svend Peter Klinken

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  1. Louise Natalie Winteringham
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Correspondence to Svend Peter Klinken.

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Winteringham, L., Kobelke, S., Williams, J. et al. Myeloid Leukemia Factor 1 inhibits erythropoietin-induced differentiation, cell cycle exit and p27Kip1 accumulation. Oncogene 23, 5105–5109 (2004). https://doi.org/10.1038/sj.onc.1207661

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