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A tripartite motif protein TRIM11 binds and destabilizes Humanin, a neuroprotective peptide against Alzheimer's disease‐relevant insults
Abstract
Humanin (HN) is a newly identified neuroprotective peptide that specifically suppresses Alzheimer's disease (AD)‐related neurotoxicity. HN peptide has been detected in the human AD brain as well as in mouse testis and colon by immunoblot and immunohistochemical analyses. By means of yeast two‐hybrid screening, we identified TRIM11 as a novel HN‐interacting protein. TRIM11, which is a member of protein family containing a tripartite motif (TRIM), is composed of a RING finger domain, which is a putative E3 ubiquitin ligase, a B‐box domain, a coiled‐coil domain and a B30.2 domain. Deletion of the B30.2 domain in TRIM11 abolished the interaction with HN, whereas the B30.2 domain alone did not interact with HN. For their interaction, at least the coiled‐coil domain was indispensable together with the B30.2 domain. The intracellular level of glutathione S‐transferase‐fused or EGFP‐fused HN peptides or plain HN was drastically reduced by the coexpression of TRIM11. Disruption of the RING finger domain by deleting the first consensus cysteine or proteasome inhibitor treatment significantly diminished the effect of TRIM11 on the intracellular level of HN. These results suggest that TRIM11 plays a role in the regulation of intracellular HN level through ubiquitin‐mediated protein degradation pathways.
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“Although there are no reports relating TRIM22 with AD, TRIM11, another member of this family, was shown to bind to and destabilize humanin, a neuroprotective peptide that suppresses AD-related neurotoxicity.49”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [49]
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Metadata
- Authors
- Niikura, T., Hashimoto, Y., Tajima, H., Ishizaka, M., Yamagishi, Y., Kawasumi, M., Nawa, M., Terashita, K., Aiso, S., & Nishimoto, I.
- Affiliations
- Keio University (JP)
- Corresponding author
- Niikura, Takako
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2003-03
- Volume
- 17
- Issue
- 6
- Pages
- 1150-1158
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2076514957
- Cited by
- 115
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 4
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TRIM11, humanin, Alzheimer's disease, neuroprotection, protein-protein interaction, B30.2 domain, coiled-coil domain, RING E3 ubiquitin ligase, ubiquitin-mediated proteolysis, neurotoxicity, protein stability
- MeSH terms
- Alzheimer Disease, Animals, Carrier Proteins, Membrane Proteins, Proteins, Yeasts, Immunoblotting, Polymerase Chain Reaction, Neuroprotective Agents, Two-Hybrid System Techniques, Ubiquitin, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice
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