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

Xiaolong Yang, Garry Chernenko, Yawei Hao, Zhihu Ding, Mary M. Pater, Alan Pater, Shou-Ching Tang

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)981-989
Number of pages9
JournalOncogene
Volume17
Issue number8
DOIs
StatePublished - Aug 27 1998

Keywords

  • Alternative translation initiation
  • Cancer
  • Four hBAG-1 isoforms
  • Overexpression
  • Subcellular localization

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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