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Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins

Abstract

Myeloid leukemia factor 1 (MLF1) is associated with the development of leukemic diseases such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, information on the physiological function of MLF1 is limited and mostly derived from studies identifying MLF1 interaction partners like CSN3, MLF1IP, MADM, Manp and the 14-3-3 proteins. The 14-3-3-binding site surrounding S34 is one of the only known functional features of the MLF1 sequence, along with one nuclear export sequence (NES) and two nuclear localization sequences (NLS). It was recently shown that the subcellular localization of mouse MLF1 is dependent on 14-3-3 proteins. Based on these findings, we investigated whether the subcellular localization of human MLF1 was also directly 14-3-3-dependent. Live cell imaging with GFP-fused human MLF1 was used to study the effects of mutations and deletions on its subcellular localization. Surprisingly, we found that the subcellular localization of full-length human MLF1 is 14-3-3-independent, and is probably regulated by other as-yet-unknown proteins.

Abbreviations

AML:

acute myeloid leukemia

CMV:

cytomegalovirus

CSN3:

subunit 3 of the COP9 signalosome

DMEM:

Dulbecco’s modified Eagle’s medium

GFP:

green fluorescent protein

MADM:

MLF1 adaptor molecule

Manp:

MLF1-associated nuclear protein

MDS:

myelodysplastic syndrome

MLF1:

myeloid leukemia factor 1

MLF1IP:

MLF1-interacting protein

NES:

nuclear export sequence

NLS:

nuclear localization signal

NPM:

nucleophosmin

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Correspondence to Christian Ottmann.

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Molzan, M., Ottmann, C. Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins. Cell Mol Biol Lett 18, 137–148 (2013). https://doi.org/10.2478/s11658-012-0044-1

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  • DOI: https://doi.org/10.2478/s11658-012-0044-1

Key words

  • MLF1
  • 14-3-3
  • Binding site
  • Protein-protein interactions
  • Subcellular localization
  • Acute myeloid leukemia
  • Myelodysplastic syndrome
  • Site-directed mutagenesis
  • Confocal microscopy
  • Live cell imaging