BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa pro
tein that bound to and enhanced the anti-apoptotic properties of Bcl-2, BAG
-1 exists as three major isoforms (designated p50, p46 and p36 or BAG-1L, B
AG-1M and BAG-1S respectively) and one minor isoform (p29), which are trans
lated from a common transcript. The differing amino terminus determines bot
h the intracellular location and the repertoire of binding partners of the
isoforms which play different roles in a variety of cellular processes incl
uding signal transduction, heat shock, apoptosis and transcription. Althoug
h in vitro data suggest that the four BAG-1 isoforms are translated by leak
y scanning, the patterns of isoform expression ill vivo, especially in tran
sformed cells, do not support this hypothesis. We have performed in vivo an
alysis of the BAG-1 5' untranslated region and shown that translation initi
ation of the most highly expressed isoform (p36/BAG-1S) can occur by both i
nternal ribosome entry and cap-dependent scanning. Following heat shock, wh
en there is a downregulation of cap-dependent translation, the expression o
f the p36 isoform of BAG-1 is maintained by internal ribosome entry.