cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP.
Myelodysplasia/acute myeloid leukemia (MDS/AML) is characterized by a t(3;5)(q25.1;q34) chromosomal translocation that forms a fusion gene between nucleophosmin (NPM) and MDS/myeloid leukemia factor 1 (MLF1). We identified a novel protein, MLF1-interacting protein (MLF1IP), that specifically associates with MLF1 by yeast two-hybrid analysis and in pulldown assays, and colocalizes with it in both the nuclei and cytoplasm of cells. The MLF1IP gene locus is at chromosome 4q35.1 and is composed of 14 exons spanning 75.8 kb of genomic DNA. The MLF1IP cDNA encodes a 46-kDa protein that contains two bipartite and two classical nuclear localization signals, two nuclear receptor-binding motifs (LXXLL), two leucine zippers, two PEST residues and several potential phosphorylation sites. MLF1IP transcripts are expressed in a variety of tissues (e.g. fetal liver, bone marrow, thymus and testis). MLF1IP appears to be a lineage-specific gene whose expression is confined exclusively to the CFU-E erythroid precursor cells, but not in mature erythrocytes. These observations, together with previous data demonstrating a role for MLF1 in suppressing red cell maturation, suggest a possible role for MLF1IP and MLF1 deregulation in the genesis of erythroleukemias.
Hanissian
Silva H
SH
Department of Neurosurgery, The University of Tennessee Health Science Center, 847 Monroe, Room 427, Memphis, TN 38163, USA. shanissi@utmem.edu
Akbar
Umar
U
Teng
Bin
B
Janjetovic
Zorica
Z
Hoffmann
Anne
A
Hitzler
Johann K
JK
Iscove
Norman
N
Hamre
Kristin
K
Du
Xiaoping
X
Tong
Yiai
Y
Mukatira
Suraj
S
Robertson
Jon H
JH
Morris
Stephan W
SW
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006657:Histones; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C485917:CENPU protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006657:Histones; C100852:MLF1 protein, human; D009687:Nuclear Proteins; D011506:Proteins