Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Breast Neoplasms / pathology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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HSC70 Heat-Shock Proteins / metabolism*
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Peptide Fragments / analysis
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Peptide Fragments / chemistry*
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Peptide Fragments / pharmacology*
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Protein Binding / drug effects
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Surface Plasmon Resonance
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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BCL2-associated athanogene 1 protein
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DNA-Binding Proteins
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HSC70 Heat-Shock Proteins
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Peptide Fragments
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Transcription Factors