CHARACTERIZATION OF A1, A NOVEL HEMATOPOIETIC-SPECIFIC EARLY-RESPONSEGENE WITH SEQUENCE SIMILARITY TO BCL-2

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates h emopoietic cell proliferation, differentiation, and functional activat ion by inducing the expression of specific genes. As part of an invest igation of the regulation of gene expression by GM-CSF, we have previo usly identified a novel murine GM-CSF-inducible gene, A1. In this repo rt, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression p attern of the gene. The results demonstrate that A1 is a hemopoietic t issue-specific gene that is expressed in several hemopoietic cell line ages, 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 induc tion of A1 mRNA accumulation was observed in response to LPS in macrop hages. This induction is not mediated by IL-1alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 g ene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encode s 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 wh ose expression is associated with a variety of stimuli and occurs in s everal hemopoietic cell types.