Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein
Abstract
Manipulation of protein stability with small molecules is a challenge in the field of drug discovery. Here we show that cellular retinoic acid binding protein-II (CRABP-II) can be specifically degraded by a novel compound, SNIPER-4, consisting of (--)-N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butyryl]-L-leucine methyl ester and all-trans retinoic acid that are ligands for cellular inhibitor of apoptosis protein 1 (cIAP1) and CRABP-II, respectively. Mechanistic analysis revealed that SNIPER-4 induces cIAP1-mediated ubiquitylation of CRABP-II, resulting in the proteasomal degradation. The protein knockdown strategy employing the structure of SNIPER-4 could be applicable to other target proteins.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Bestatin binds BIRC2 with moderate affinity and induces its auto-ubiquitylation and degradation.
“bestatin, which binds BIRC2 with moderate affinity and induces its auto-ubiquitylation and degradation”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [120]
The citation lists haven’t been fetched yet
References 18 · Cited by 118
- Authors
- Okuhira, K., Ohoka, N., Sai, K., Nishimaki-Mogami, T., Itoh, Y., Ishikawa, M., Hashimoto, Y., & Naito, M.
- Affiliations
- National Institute of Health Sciences (JP)
- The University of Tokyo (JP)
- Corresponding author
- Naito, Mikihiko
- ORCID
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2011-03-15
- Volume
- 585
- Issue
- 8
- Pages
- 1147-1152
- ISSN
- 0014-5793 (ISSN-L)
- OpenAlex
- W2015273986
- Cited by
- 118
- References
- 18
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 13 · 2021: 11 · 2020: 19 · 2019: 17 · 2018: 11 · 2017: 12 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 1
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nippon Kayaku Co. Ltd.
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Astellas Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- CRABP2, cIAP1, ubiquitination, proteasomal degradation, hybrid molecules, protein stability, all-trans retinoic acid, protein-protein cross-linking, structure-based drug design
- MeSH terms
- Cross-Linking Reagents, Humans, Leucine, Tretinoin, Immunoblotting, Receptors, Retinoic Acid, RNA Interference, Cell Line, Tumor, Proteasome Endopeptidase Complex, Inhibitor of Apoptosis Proteins, Ubiquitination, Protein Stability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
