Cloning, mapping and expression of PEBP2αC, a third gene encoding the mammalian Runt domain

Abstract PEBP2/CBF is a heterodimeric transcription factor composed of α and β subunits. Previously, we reported two distinct mouse genes, PEBP2αA and PEBP2αB, which encode the α subunit. PEBP2αB is the homologue of human AML1, encoding the acute myeloid leukemia 1 protein. AMLI and human PEBP2/CBFβ were detected independently at the breakpoints of two characteristic chromosome translocations observed frequently in two subtypes of acute myeloid leukemia. The PEBP2α proteins contain a 128-amino-acid (aa) region highly homologous to the Drosophila melanogaster segmentation gene runt. The evolutionarily conserved region, named the Runt domain, harbors DNA-binding and heterodimerizing activities. In this study, we identified the third Runt-domain-encoding gene, PEBP2αC, which maps to lp36.11-p36.13 in the human chromosome and encodes a 415-aa protein. PEBP2αC forms a heterodimer with PEBP2β, binds to the PEBP2 site and transactivates transcription, similar to PEBP2αA and PEBP2αB.

[1]  M. Kozak An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. , 1987, Nucleic acids research.

[2]  Y. Ito,et al.  PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  N. Speck,et al.  Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor , 1993, Molecular and cellular biology.

[4]  Y. Yamaguchi-Iwai,et al.  Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. , 1993, Oncogene.

[5]  E. Nishida,et al.  65-kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites. , 1990, Biochemistry.

[6]  J. Gergen,et al.  The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system. , 1990, Genes & development.

[7]  M. Ohki,et al.  The Runt domain identifies a new family of heteromeric transcriptional regulators. , 1993, Trends in genetics : TIG.

[8]  M. Ohki,et al.  t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  N. Copeland,et al.  PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials , 1994, Molecular and cellular biology.

[10]  M. Leppert,et al.  Mapping of the MYC gene to band 8q24.12----q24.13 by R-banding and distal to fra(8)(q24.11), FRA8E, by fluorescence in situ hybridization. , 1991, Cytogenetics and cell genetics.

[11]  M. Ashburner A Laboratory manual , 1989 .

[12]  Y. Sakaki,et al.  The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene. , 1989, Gene.

[13]  F. Collins,et al.  Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. , 1993, Science.

[14]  Yoshiaki Ito,et al.  Molecular Cloning and Characterization of PEBP2β, the Heterodimeric Partner of a Novel Drosophila runt-Related DNA Binding Protein PEBP2α , 1993 .

[15]  H. Drabkin,et al.  Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. , 1992, Blood.