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).

More general terms

• DNA-binding protein
• phosphoprotein

Additional terms

• myelodysplastic syndrome (MDS)
• myeloid leukemia

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4291
• OMIM: https://mirror.omim.org/entry/601402
• UniProt: http://www.uniprot.org/uniprot/P58340.html