BAG-1 expression and function in human cancer

Abstract

BAG-1 is a multifunctional protein that interacts with a wide range of target molecules to regulate apoptosis, proliferation, transcription, metastasis and motility. Interaction with chaperone molecules may mediate many of the effects of BAG-1. The pathways regulated by BAG-1 play key roles in the development and progression of cancer and determining response to therapy, and there has been considerable interest in determining the clinical significance of BAG-1 expression in malignant cells. There is an emerging picture that BAG-1 expression is frequently altered in a range of human cancers relative to normal cells and a recent report suggests the exciting possibility that BAG-1 expression may have clinical utility as a prognostic marker in early breast cancer. However, other studies of BAG-1 expression in breast cancer and other cancer types have yielded differing results. It is important to view these findings in the context of current knowledge of BAG-1 expression and function. This review summarises recent progress in understanding the clinical significance of BAG-1 expression in cancer in light of our understanding of BAG-1 function.

Figure 1

Schematic diagram of the human BAG-1 isoforms. The BAG-1 mRNA and the position of the alternate translation initiation sites that give rise to the three human BAG-1 isoforms is shown at the top. The domain structure of the BAG-1 isoforms is shown underneath (NLS, nuclear localization sequence; ULD, ubiquitin-like domain).

Figure 2

BAG-1 binding partners and functions. BAG-1 interaction partners are indicated. Some of these interactions are direct, whereas others are probably mediated via binding to chaperone molecules, e.g., NHR. Interactions of BAG-1 with chaperones, E3 ligases and the proteasome suggest a key role in regulating the ubiquitin/proteasomal degradation system. Biological activities ascribed to BAG-1 are indicated below along with some potential molecular targets that might contribute to these effects. However, it is important to note that definitive evidence linking specific BAG-1 target molecules to biological responses is often lacking.