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

摘要

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. Structured summary: MINT-7265269, MINT-7265296, MINT-7265324, MINT-7265339, MINT-7265351, MINT-7265364, MINT-7265483, MINT-7265464, MINT-7265310: HSC70 (uniprotkb:P11142) binds (MI:0407) to BAG1 (uniprotkb:Q99933) by peptide array (MI:0081). MINT-7265281: peptide 15L (uniprotkb:Q99933) binds (MI:0407) to HSC70 (uniprotkb:P11142) by surface plasmon resonance (MI:0107). © 2009 Federation of European Biochemical Societies.