Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia.
Chromosome region 11q23 is involved in reciprocal chromosome translocations associated with human acute leukemias. These aberrations fuse the ALL-1 gene located at 11q23 to a series of partner genes positioned on a variety of human chromosomes. The fused genes encode chimeric proteins. Here we report the cloning and characterization of the ALL-1 partner at 17q21, the AF17 gene. The AF17 gene encodes a protein of 1093 amino acids, containing a leucine-zipper dimerization motif located 3' of the fusion point and a cysteine-rich domain at the N terminus. The latter can be arranged in three zinc fingers and shows homology to a domain within the protein Br140 (peregrin). AF17 contains stretches of amino acids previously associated with domains involved in transcriptional repression or activation. Based on features of AF17 and of the proteins encoded by the other partner genes analyzed and in conjunction with other recent studies, we propose a model in which ALL-1 rearrangements result in loss of function of the gene. In this model, the partner polypeptide plays an accessory role either by repressing activity of the truncated ALL-1 protein or by blocking the function of the normal protein presumably present in the leukemic cells.
Prasad
R
R
Jefferson Cancer Institute, Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107.
Leshkowitz
D
D
Gu
Y
Y
Alder
H
H
Nakamura
T
T
Saito
H
H
Huebner
K
K
Berger
R
R
Croce
C M
CM
Canaani
E
E
D000595:Amino Acid Sequence; D001483:Base Sequence; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005091:Exons; D015321:Gene Rearrangement; D006801:Humans; D016350:Leucine Zippers / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; C096106:MLLT6 protein, human; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA