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myeloid leukemia factor 1; myelodysplasia-myeloid leukemia factor 1 (MLF1)
Function:
- may play a role in normal hemopoietic differentiation & in erythroid/myeloid lineage switching
- interferes with erythopoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels
- suppresses RFWD2/COP1 activity via CSN3 which activates p53 & induces cell cycle arrest
- binds DNA & affects the expression of a number of genes so may function as a transcription factor in the nucleus
- phosphorylation is required for binding to YWHAZ
- interacts with MLF1IP, NRBP1/MADM, YWHAZ/14-3-3-zeta & HNRPUL2/MANP
- NRBP1 recruits a serine kinase which phosphorylates both itself & MLF1
- phosphorylated MLF1 then binds to YWHAZ & is retained in the cytoplasm
- retained in the nucleus by binding to HNRPUL2
- binds to COPS3/CSN3 which is required for suppression of RFWD2 & activation of p53
Structure:
- belongs to the MLF family
Compartment:
- cytoplasm, nucleus
- in non-hematopoietic cells, resides primarily in the cytoplasm with some punctate nuclear localization
- shuttles between the cytoplasm & nucleus
- in hematopoietic cells, located preferentially in the nucleus
- found in the nucleolus when fused to NPM
Expression:
- most abundant in testis, ovary, skeletal muscle, heart, kidney & colon
- low expression in spleen, thymus & peripheral blood leukocytes
Pathology:
- chromosomal translocation t(3;5)(q25.1;q34) involving MLF1 results in a NPM-MLF1 fusion protein, responsible for myelodysplastic syndrome (MDS) which progresses to acute myeloid leukemia (AML).
Related
MLF1 gene; MLF1 myeloid leukemia factor 1 gene; myelodysplasia-myeloid leukemia factor 1 gene
myelodysplastic syndrome (MDS)
myeloid leukemia
General
DNA-binding protein
phosphoprotein
Properties
SIZE: entity length = 268 aa
MW = 31 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: breakpoint {16-17}
COPS3 interaction {50-125}
DNA-binding motif
phosphorylation site
Database Correlations
OMIM 601402
UniProt P58340
Pfam PF10248
Entrez Gene 4291
References
- UniProt :accession P58340
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/MLF1.html