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

Winteringham, L.N., Kobelke, S., Williams, J.H., Ingley, E. and Klinken, S.P. (2004) Myeloid Leukemia Factor 1 inhibits erythropoietin-induced differentiation, cell cycle exit and p27Kip1 accumulation. Oncogene, 23 (29). pp. 5105-5109.

Free to read: https://doi.org/10.1038/sj.onc.1207661
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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 Cull and Skp2, components of the ubiquitin E3 ligase complex SCFSkp2 involved in the proteasomal degradation of p27 Kip1. In contrast, Mlf1 did not interfere with increases in p27 Kip1 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.

Publication Type: Journal Article
Publisher: Nature Publishing Group
URI: http://researchrepository.murdoch.edu.au/id/eprint/39568
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