ArticleMolecular cell2009
Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2.
Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 179 citations in OpenAlex.
- CDT1 acts with the replisome to remodel replication forks.Science advances · 2026Article
- Stability of c-Myc Protein in Early S Phase Is Regulated by the Interaction with PCNA.International journal of molecular sciences · 2026Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Extreme multivalency and a composite short linear motif facilitate PCNA-binding, localisation and abundance of p21 (CDKN1A).The FEBS journal · 2025Article
- Modulation of the malignant behavior of tongue squamous cell carcinoma cells by matrix metallopeptidase 25 through the NF-κB pathway.Histology and histopathology · 2025Article
- Versatile enhancement of the killing potential of anti-cancer agents achieved by peptide mimetics of the PCNA interface towards specialized DNA polymerases.Cell death & disease · 2025Article
- Article
- The bacterial DNA sliding clamp, β-clamp: structure, interactions, dynamics and drug discovery.Cellular and molecular life sciences : CMLS · 2024Review
- Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.Nucleic acids research · 2024Article
- DCAF14 regulates CDT2 to promote SET8-dependent replication fork protection.Life science alliance · 2024Article
- Silencing circSERPINE2 restrains mesenchymal stem cell senescence via the YBX3/PCNA/p21 axis.Cellular and molecular life sciences : CMLS · 2023Article
- Elucidation of E3 ubiquitin ligase specificity through proteome-wide internal degron mapping.Molecular cell · 2023Article
- A FRET-Based Assay for the Identification of PCNA Inhibitors.International journal of molecular sciences · 2023Article
- Multi-range ERK responses shape the proliferative trajectory of single cells following oncogene induction.Cell reports · 2023Article
- The cohesin modifier ESCO2 is stable during DNA replication.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Article
- CDT1 inhibits CMG helicase in early S phase to separate origin licensing from DNA synthesis.Molecular cell · 2023Article
- Non-canonical binding of the Chaetomium thermophilum PolD4 N-terminal PIP motif to PCNA involves Q-pocket and compact 2-fork plug interactions but no 3The FEBS journal · 2023Article
- Canonical binding ofFrontiers in molecular biosciences · 2023Article
- PCR cloning Intermediated Gibson assembly (PIG) for Constructing DNA Repair Templates in CRISPR-Cas9 Based Gene Editing.microPublication biology · 2023Article
- Unorthodox PCNA Binding by Chromatin Assembly Factor 1.International journal of molecular sciences · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Substrates of the E3 ubiquitin ligase CRL4(Cdt2), including Cdt1 and p21, contain a PCNA-binding motif called a PIP box. Upon binding of the PIP box to PCNA on chromatin, CRL4(Cdt2) is recruited and the substrate is ubiquitylated. Importantly, a PIP box cannot be sufficient for destruction, as most PIP box proteins are stable. Using Xenopus egg extracts, we identify two sequence elements in CRL4(Cdt2) substrates that promote their proteolysis: a specialized PIP box that confers exceptionally efficient PCNA binding and a basic amino acid 4 residues downstream of the PIP box, which recruits CRL4(Cdt2) to the substrate-PCNA complex. We also identify two mechanisms that couple CRL4(Cdt2)-dependent proteolysis to the chromatin-bound form of PCNA, ensuring that this proteolysis pathway is active only in S phase or after DNA damage. Thus, CRL4(Cdt2) recognizes an unusual degron, which is assembled specifically on chromatin via the binding of a specialized PIP box to PCNA.
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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.