Abstract
E2A-PBX1 is a chimeric gene formed by the t(1;19)(q23;p13.3) chromosomal translocation of pediatric pre-B-cell leukemia. The E2A-Pbx1 fusion protein contains sequences encoding the transactivation domain of E2A joined to a majority of the Pbx1 protein, which contains a novel homeodomain. Earlier, we found that expression of E2A-Pbx1 causes malignant transformation of NIH 3T3 fibroblasts and induces myeloid leukemia in mice. Here we demonstrate that the homeodomains encoded by PBX1, as well as by the highly related PBX2 and PBX3 genes, bind the DNA sequence ATCAATCAA. E2A-Pbx1 strongly activates transcription in vivo through this motif, while Pbx1 does not. This finding suggests that E2A-Pbx1 transforms cells by constitutively activating transcription of genes regulated by Pbx1 or by other members of the Pbx protein family.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenovirus E2 Proteins / biosynthesis
-
Adenovirus E2 Proteins / metabolism*
-
Amino Acid Sequence
-
Base Sequence
-
Binding Sites
-
Chromosomes, Human, Pair 1*
-
Chromosomes, Human, Pair 19*
-
Consensus Sequence
-
DNA / metabolism
-
DNA Primers
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / metabolism*
-
Gene Rearrangement
-
Genes, Homeobox
-
Glutathione Transferase / biosynthesis
-
Glutathione Transferase / metabolism
-
Humans
-
Molecular Sequence Data
-
Multigene Family
-
Oligodeoxyribonucleotides
-
Point Mutation
-
Polymerase Chain Reaction
-
Pre-B-Cell Leukemia Transcription Factor 1
-
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / metabolism*
-
Recombinant Fusion Proteins / biosynthesis
-
Recombinant Fusion Proteins / metabolism
-
Transcription, Genetic*
-
Translocation, Genetic*
Substances
-
Adenovirus E2 Proteins
-
DNA Primers
-
DNA-Binding Proteins
-
Oligodeoxyribonucleotides
-
Pre-B-Cell Leukemia Transcription Factor 1
-
Proto-Oncogene Proteins
-
Recombinant Fusion Proteins
-
PBX1 protein, human
-
DNA
-
Glutathione Transferase