Tumor cells very often have elevated expression of HSP70, the anti-apoptotic properties of which contribute to overall
tumor survival. Independent of its anti-apoptotic properties, HSP70 was also suggested to be involved in the antigen presentation process by chaperoning cytosolic
peptides, thus protecting them from rapid degradation and securing the
peptide pool for further processing. In this study, we identified a 33-amino
acid N-terminal
dermcidin (
DCD)-derived
peptide from the repertoire of in vivo HSP70-associated
peptides isolated from a leukemic cell line, K562. The
DCD peptide has been previously shown to be involved in
tumorigenesis, to increase
tumor survival rate, to improve
tumor stress resistance, and to aid growth. We show that HSP70 is a specific binding partner for the
DCD prosurvival
peptide and define an
ATP-dependent
DCD-binding site (GNPCH). We also identify an
HLA-A*03 antigenic
epitope within the
DCD peptide, which follows and partially overlaps the HSP70-binding site (CHEASAAQK). This study describes the interaction between HSP70 and the
DCD-derived prosurvival
peptide, an interaction that may direct the
peptide toward antigen presentation and independently contribute to the prosurvival mechanism mediated by
DCD.