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.
Highlights
Myeloid leukemia factor 1 (MLF1) is a 30-kDa protein that became of interest because of its association with the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)
The nuclear localization suggested that the transforming activity of MLF1 in AML was due to its ectopic expression, which may cause an enhanced interaction with nuclear protein partners [10]
Taking into account the findings reported for the mouse homologue of MLF1 [11], we hypothesized that the biological function of 14-3-3 binding to human MLF1 could be the control of its nuclear import and export
Summary
Myeloid leukemia factor 1 (MLF1) is a 30-kDa protein that became of interest because of its association with the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). MLF1 localizes to the cytoplasm in non-hemopoietic cells [8], it preferentially resides in the nucleus of hemopoietic cells [8,9,10,11] Beyond these reports, information on the physiological function of MLF1 is limited and is derived mostly from studies identifying MLF1 interaction partners, such as CSN3 [12], MLF1IP [13, 14], MADM [15], Manp, and the 14-3-3 proteins [11, 5,6,7,8,9,10,11,12,13,14,15,16,17]. 14-3-3 proteins regulate the activity of the cellcycle phosphatase Cdc25 [22, 23], the protein kinase C-RAF [24, 25] and the transcriptional modulator YAP [26, 27], and stabilize the tumour suppressor p53 [28, 29]. 14-3-3 proteins have been associated with various cancers [30], the virulence of human pathogenic organisms [31, 32], and the development of neurodegenerative diseases [33]
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