BAG-1 is a multifunctional protein that is expressed in most cells. Originally identified as a Bcl-2 binding protein [
1], other interaction partners of BAG-1 were described, including the serine threonine kinase C-Raf [
2]. The C-terminal "BAG domain" of BAG-1 mediates the interaction with the Hsc70 and Hsp70 heat shock proteins [
3], molecular chaperones that bind proteins in non-native states assisting them to reach a functional active conformation [
4]. BAG-1 acts as a nucleotide exchange factor in this activation cycle [
3]. The above findings indicated that BAG-1 might connect protein folding with other signaling pathways. Signaling networks promoting cell growth and proliferation are frequently deregulated in cancer [
5]. The classical mitogenic cascade transmits stimuli from growth factor receptors via Ras, Raf, MEK and ERK to the cell nucleus [
6]. C-Raf, like A- and B-Raf kinases also act at the outer membrane of mitochondria to augment cell survival [
7,
8]. Previously we had observed the stimulation of C-Raf kinase activity by BAG-1 in vitro [
2]. Ras and B-Raf mutations have been found in various human cancers [
9,
10]. Evidence that BAG-1 expression is frequently altered in human cancers, in particular in breast cancer, relative to normal cells has been put forward but the notion that overexpression of BAG-1 contributes to poor prognosis in tumorigenesis remains controversial [
11].