biostudies-literatureHarr MWNCI NIH HHS165-177https://www.ebi.ac.uk/biostudies/studies/S-EPMC10569261biostudies-literatureUnknown7(3)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 killiArchives of microbiology & immunologyA Novel Peptide that Disrupts the Lck-IP₃R Protein-Protein Interaction Induces Widespread Cell Death in Leukemia and Lymphoma.PMC10569261R01 CA042755T32 CA059366Harr MWHaberer BZhong FAldabbagh KYee VLavik AMcColl KDistelhorst CWfalseA Novel Peptide that Disrupts the Lck-IP₃R Protein-Protein Interaction Induces Widespread Cell Death in Leukemia and Lymphoma.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 killi2023-01-01T00:00:00Z20232025-04-26T15:10:01.779Z2024-11-21T09:48:19.787ZS-EPMC105692613782957110.26502/ami.936500114