A Novel Peptide that Disrupts the Lck-IP₃R Protein-Protein Interaction Induces Widespread Cell Death in Leukemia and Lymphoma.

ABSTRACT: There is increasing evidence that the T-cell protein, Lck, is involved in the pathogenesis of chronic lymphocytic leukemia (CLL) as well as other leukemias and lymphomas. We previously discovered that Lck binds to domain 5 of inositol 1,4,5-trisphosphate receptors (IP₃R) to regulate Ca²⁺ homeostasis. Using bioinformatics, we targeted a region within domain 5 of IP₃R-1 predicted to facilitate protein-protein interactions (PPIs). We generated a synthetic 21 amino acid peptide, KKRMDLVLELKNNASKLLLAI, which constitutes a domain 5 sub-domain (D5SD) of IP₃R-1 that specifically binds Lck via its SH2 domain. With the addition of an HIV-TAT sequence to enable cell permeability of D5SD peptide, we observed wide-spread, Ca²⁺-dependent, cell killi

SUBMITTER: Harr MW 

PROVIDER: S-EPMC10569261 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature