ArticleProceedings of the National Academy of Sciences of the United States of America2003
Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 273 citations in OpenAlex.
- Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.Cell death & disease · 2017Trial
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- Age-diet interactions significantly influence intratumoral gene expression, gut microbiome signature and tumor microenvironment in colorectal cancer.Neoplasia (New York, N.Y.) · 2025Article
- HNF1α-Q125ter-mediated mitochondrial dysfunction and impaired mitophagy in β-cells.Journal of molecular endocrinology · 2025Article
- HUMANIN produced by human efferocytic macrophages promotes the resolution of inflammation.Cell death & disease · 2025Article
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Mitochondrial-derived microproteins: from discovery to function.Trends in genetics : TIG · 2025Review
- Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin-Nox2 interaction in cardioprotection.Frontiers in nutrition · 2025Article
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.Protein and peptide letters · 2025Review
- Role of IGFBP-3 in Human Diseases Relying on Different Cell Signaling Pathways.Advanced biomedical research · 2025Review
- Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology.Aging cell · 2024Article
- Humanin activates integrin αV-TGFβ axis and leads to glioblastoma progression.Cell death & disease · 2024Article
- Review
- Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.Peptides · 2024Review
- Humanin Treatment Protects Against Venetoclax-Induced Bone Growth Retardation inJournal of the Endocrine Society · 2024Article
- Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.Biology · 2023Review
- Microproteins-Discovery, structure, and function.Proteomics · 2023Review
- Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions.International journal of obesity (2005) · 2023Review
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell growth and 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 a 24-aa peptide that has been shown to specifically inhibit neuronal cell death induced by familial Alzheimer's disease mutant genes and amyloid-beta (Abeta). The physical interaction of HN with IGFBP-3 was determined to be of high affinity and specificity and was confirmed by yeast mating, displaceable pull-down experiments with (His)-6-tagged HN, and ligand blot experiments. Co-immunoprecipitation of IGFBP-3 and HN from mouse testes confirmed the interaction in vivo. In cross-linking experiments, HN bound IGFBP-3 but did not compete with IGF-I-IGFBP-3 binding; competitive ligand dot blot experiments revealed the 18-aa heparin-binding domain of IGFBP-3 as the binding site for HN. Alanine scanning determined that F6A-HN mutant does not bind IGFBP-3. HN but not F6A-HN inhibited IGFBP-3-induced apoptosis in human glioblastoma-A172. In contrast, HN did not suppress IGFBP-3 response in SH-SY5Y neuroblastoma and mouse cortical primary neurons. In primary neurons, IGFBP-3 markedly potentiated HN rescue ability from Abeta1-43 toxicity. In summary, we have identified an interaction between the survival peptide HN and IGFBP-3 that is pleiotrophic in nature and is capable of both synergistic and antagonistic interaction. This interaction may prove to be important in neurological disease processes and could provide important targets for drug development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.