The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
β-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases
Open accessAbstract
β-TrCP, the F-box protein of the SCF β-TrCP ubiquitin ligase (SCF, Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif (DpSGΦXpS) in various SCF β-TrCP target proteins. The Cdc25A phosphatase, a key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin-dependent degradation in response to genotoxic stress. β-TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk1 and other unknown kinases. However, Xenopus Cdc25A does not have a DSG motif at the corresponding site of human Cdc25A. Here, we report that both Xenopus Cdc25A and human Cdc25A have a previously undescribed nonphosphorylated DDG motif (DDGΦXD) for recognition by β-TrCP. When analyzed by using Xenopus eggs, the binding of β-TrCP to the DDG motif is essential for the Chk1-induced ubiquitination and degradation of Xenopus Cdc25A and also plays a role in the degradation of human Cdc25A. The DDG motif also exists in human Cdc25B phosphatase (another key cell-cycle regulator), binds β-TrCP strongly, and is essential for the ubiquitination and degradation of the (labile) phosphatase in normal conditions. We provide strong evidence that, in both Cdc25A and Cdc25B, the binding (efficiency) of β-TrCP to the DDG motif is regulated by nearby residues, while ubiquitination is regulated by other events in addition to the β-TrCP binding. Finally, our additional data suggest that β-TrCP may recognize nonphosphorylated DDG-like motifs in many other proteins, including X11L (a putative suppressor of β-amyloid production) and hnRNP-U (a pseudosubstrate of SCF β-TrCP ).
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“The occurrence of DNA damage response in G2-phase, leads to checkpoint mediator (claspin) dependent activation of Chk1/2, followed by SCFβTrcP mediated degradation of CDK-activating phosphatase Cdc25A [341, 342], that results in arrest of multiple cell-cycle transition including the G2 checkpoint [343, 344].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [342]
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Metadata
- Authors
- Kanemori, Y., Uto, K., & Sagata, N.
- Affiliations
- Kyushu University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-04-21
- Volume
- 102
- Issue
- 18
- Pages
- 6279-6284
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1083676
- OpenAlex
- W2110323618
- Cited by
- 128
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 2 · 2012: 6
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- dx.doi.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- β-TrCP, SCF ubiquitin ligase, CDC25A, CDC25B, ubiquitination, protein degradation, Chk1, genotoxic stress, cell cycle regulation, HNRNPU
- MeSH terms
- Checkpoint Kinase 1, Animals, Glutathione Transferase, Humans, Ovum, Protein Binding, Protein Kinases, Ubiquitins, Xenopus, Immunoblotting, Mutagenesis, DNA, Complementary, Cell Cycle Proteins, cdc25 Phosphatases, Amino Acid Motifs, Xenopus Proteins, Ubiquitin-Protein Ligases, beta-Transducin Repeat-Containing Proteins
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