Short peptides derived from the BAG-1 C-terminus inhibit the interaction between BAG-1 and HSC70 and decrease breast cancer cell growth.

BAG-1, a multifunctional protein, interacts with a plethora of cellular targets where the interaction with HSC70 and HSP70, is considered vital. Structural studies have demonstrated the C-terminal of BAG-1 forms a bundle of three alpha-helices of which helices 2 and 3 are directly involved in binding to the chaperones. Here we found peptides derived from helices 2 and 3 of BAG-1 interfered with BAG-1:HSC70 binding. We confirmed that a 12 amino-acid peptide from helix 2 directly interacted with HSC70 and when introduced into MCF-7 and ZR-75-1 cells, these peptides inhibited their growth. In conclusion, we have identified a small domain within BAG-1 which appears to play a critical role in the interaction with HSC70.