Identification of a novel Bcl-2 related gene, BRAG-1, in human glioma.
Programmed cell death (apoptosis) plays a major role in embryogenesis, in mature organ homeostasis and in many disease states including cancer. Apoptosis occurs as an orderly cell-intrinsic suicide program regulated by a family of genes related to Bcl-2. Here, we describe the cloning and molecular characterization of a gene homologous to Bcl-2 from a human glioma. This gene named BRAG-1 (for brain-related apoptosis gene) has an open reading frame that encodes for a protein of 31 kDa sharing significant sequence homology with the Bcl-2 family of genes in the BH1 and BH2 regions. Northern blot analyses revealed that BRAG-1 is expressed in human gliomas as a 1.8 kb message. This gene, interestingly, was found to be expressed predominantly in normal human brain as a 4.5 kb transcript which is different in size from the message found in tumor tissues. These results suggest that BRAG-1 may be rearranged in human gliomas leading to its over-expression as a truncated transcript. Utilizing a bacterial expression vector, we produced BRAG-1 protein which was found to cross-react with a Bcl-2 monoclonal antibody, further suggesting structural and immunological similarity to Bcl-2.
Das
R
R
Department of Neurosurgery, Thomas Jefferson University Hospital-Wills Neurosensory Institute, Philadelphia, Pennsylvania 19107, USA.
Reddy
E P
EP
Chatterjee
D
D
Andrews
D W
DW
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D015870:Gene Expression; D005796:Genes / Q000235:genetics*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D017422:Sequence Analysis, DNA