A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins
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Abstract
The phosphorylation of 14-3-3 binding motif is involved in many cellular processes. A strategy that enables targeted degradation of 14-3-3-binding phosphoproteins (14-3-3-BPPs) for studying their functions is highly desirable for basic research. Here, we report a phosphorylation-induced, ubiquitin-proteasome-system-mediated targeted protein degradation (TPD) strategy that allows specific degradation of 14-3-3-BPPs. Specifically, by ligating a modified von Hippel-Lindau E3-ligase with an engineered 14-3-3 bait, we generated a protein chimera referred to as Targeted Degradation of 14-3-3-binding PhosphoProtein (TDPP). TDPP can serve as a universal degrader for 14-3-3-BPPs based on the specific recognition of the phosphorylation in 14-3-3 binding motifs. TDPP shows high efficiency and specificity to a difopein-EGFP reporter, general and specific 14-3-3-BPPs. TDPP can also be applied for the validation of 14-3-3-BPPs. These results strongly support TDPP as a powerful tool for 14-3-3 related research.
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Cites
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Flagged first, then by citations
- Authors
- Li, Z., Huang, X., Li, M., Chen, Y. E., Wang, Z., & Liu, L.
- Affiliations
- University of Michigan (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Wang, Zhong
- Liu, Liu
- Venue
- Heliyon
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 9
- Issue
- 5
- Pages
- e16318
- ISSN
- 2405-8440 (ISSN-L)
- PMC
- PMC10213371
- OpenAlex
- W4377086858
- Cited by
- 2
- References
- 7
- Citations by year
- 2024: 2
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Heliyon (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01HL139735, R01HL163672)
- 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 › 14-3-3 protein interactions
- Keywords
- targeted protein degradation, ubiquitination, ubiquitin-proteasome system, 14-3-3 binding motif, protein chimeras
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