Human BAG-1/RAP46 protein is generated as four isoforms by alternative translation initiation and overexpressed in cancer cells

Oncogene. 1998 Aug 27;17(8):981-9. doi: 10.1038/sj.onc.1202032.


Previously, a Bcl-2-interacting protein, BAG-1, was cloned from mouse cells and was shown to interact with several other proteins and to be important for inhibition of apoptosis. Human BAG-1 (hBAG-1) cDNA, recently isolated by us and two other groups, has been shown to be identical to a hormone receptor-binding protein, RAP46. However, different molecular masses of hBAG-1 protein products were noted by these three groups. Here we demonstrated that hBAG-1 protein was expressed as four isoforms, designated p50, p46, p33 and p29, with apparent molecular masses of 50 kDa, 46 kDa, 33 kDa and 29 kDa, respectively. Deletion, site-directed mutagenesis and in vitro transcription/translation analysis showed that the four protein products of hBAG-1 were expressed by alternative initiation from four different start codons through a leaky scanning mechanism. Furthermore, we demonstrated that the distinct forms of hBAG-1 have different subcellular localizations, suggesting that they may have distinct functions in the cells. Characterization of hBAG-1 RNA and protein also showed that hBAG-1 was overexpressed in human cervical, breast and lung cancer cell lines. Taken together, these data clarify the conflicting observations reported in the literature and suggest that hBAG-1 is expressed as four forms of protein products, which may play a differential role in apoptosis and oncogenesis of human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing* / genetics
  • Base Sequence
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Isomerism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Organ Specificity / genetics
  • Peptide Chain Initiation, Translational / genetics*
  • Subcellular Fractions / metabolism
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • Transcription Factors