Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2

J Immunol. 1993 Aug 15;151(4):1979-88.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF-inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bone Marrow Cells*
  • Cloning, Molecular
  • Cycloheximide / pharmacology
  • DNA / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression / drug effects
  • Genes*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Hematopoiesis*
  • Homeodomain Proteins*
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred CBA
  • Minor Histocompatibility Antigens
  • Molecular Sequence Data
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger / genetics
  • Replication Protein C
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Transcription, Genetic

Substances

  • BCL2-related protein A1
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • MATA1 protein, S cerevisiae
  • Mcl1 protein, mouse
  • Minor Histocompatibility Antigens
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA
  • Cycloheximide
  • Replication Protein C