Cell-penetrating fusion peptides OD1 and OD2 interact with Bcr–Abl and influence the growth and apoptosis of K562 cells

The Bcr–Abl oncoprotein is the cause of chronic myelogenous leukemia (CML). Crystal structure analysis suggests that Bcr 30–63 is the core of the Bcr–Abl oligomerization interface for aberrant kinase activity; however, the precise role of other residues of Bcr 1–72 excluding Bcr 30–63 have not been evaluated. In this study, Bcr 30–63 was named OD2 and other residues of Bcr 1–72 were named OD1. Cytoplasmic transduction peptide (CTP) was used to carry molecules into cytoplasm. CTP-OD1 and CTP-OD2 fusion peptides were expressed from a cold-inducible expression system. Our results demonstrated that both fusion peptides could localize into the cytoplasm, specifically interact with the Bcr–Abl protein and further inhibit growth, induce apoptosis, and decrease the phosphorylation of Bcr–Abl in K562 cell lines. However, the viability of THP-1, a Bcr–Abl negative cell line, was unaffected. These results suggested that CTP-OD1 and CTP-OD2 may be an attractive therapeutic option to inhibit the activation of Bcr–Abl kinase in CML.