Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

• DOI: 10.1073/pnas.2135111100
• Publication Date: 2003-10-29T06:26:18Z
• Authors: Maaria Ikonen; Bingrong Liu; Yuichi Hashimoto; Liqun Ma; Kuk-Wha Lee; Takako Niikura; Ikuo Nishimoto; Pinchas Cohen
• Keywords: Immunoprecipitation

Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell survival. By using a yeast two-hybrid screen to identify IGFBP-3-interacting proteins, we cloned humanin (HN) as an IGFBP-3-binding partner. HN is 24-aa peptide that has been shown specifically inhibit neuronal death induced by familial Alzheimer's disease mutant genes amyloid-β (Aβ). The physical interaction of with IGFBP-3 was determined be high affinity specificity confirmed mating, displaceable pull-down experiments (His)-6-tagged HN, ligand blot experiments. Coimmunoprecipitation from mouse testes the in vivo . In cross-linking experiments, bound but did not compete IGF-I–IGFBP-3 binding; competitive dot revealed 18-aa heparin-binding domain binding site for HN. Alanine scanning F6A-HN does bind IGFBP-3. inhibited IGFBP-3-induced apoptosis human glioblastoma-A172. contrast, suppress response SH-SY5Y neuroblastoma cortical primary neurons. neurons, markedly potentiated rescue ability Aβ 1–43 toxicity. summary, have identified between survival pleiotrophic nature capable both synergistic antagonistic interaction. This may prove important neurological processes could provide targets drug development.