ArticleEMBO reports2010
New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers Cdc2 polyubiquitination and G2 arrest under genotoxic stresses.
Article in EMBO reports, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- SENP5 drives breast cancer progression through deSUMOYlation of CDK1.Breast cancer research : BCR · 2025Article
- The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination.Cancer gene therapy · 2025Article
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.Biomolecules · 2022Review
- GPS 5.0: An Update on the Prediction of Kinase-specific Phosphorylation Sites in Proteins.Genomics, proteomics & bioinformatics · 2020Article
- Selective Autophagy Regulates Cell Cycle in Cancer Therapy.Theranostics · 2019Review
- Peptide Level Turnover Measurements Enable the Study of Proteoform Dynamics.Molecular & cellular proteomics : MCP · 2018Article
- PKR: A Kinase to Remember.Frontiers in molecular neuroscience · 2018Review
- A Novel Inhibitor IDPP Interferes with Entry and Egress of HCV by Targeting Glycoprotein E1 in a Genotype-Specific Manner.Scientific reports · 2017Article
- Lack of Casein Kinase 1 Delta Promotes Genomic Instability - The Accumulation of DNA Damage and Down-Regulation of Checkpoint Kinase 1.PloS one · 2017Article
- Eukaryotic translation initiation factor 3 subunit D overexpression is associated with the occurrence and development of ovarian cancer.FEBS open bio · 2016Article
- p53-derived host restriction of HIV-1 replication by protein kinase R-mediated Tat phosphorylation and inactivation.Journal of virology · 2015Article
- Article
- βTrCP controls the lysosome-mediated degradation of CDK1, whose accumulation correlates with tumor malignancy.Oncotarget · 2014Article
- Toll-like receptor-3 is dispensable for the innate microRNA response to West Nile virus (WNV).PloS one · 2014Article
- NF-κB-mediated degradation of the coactivator RIP140 regulates inflammatory responses and contributes to endotoxin tolerance.Nature immunology · 2012Article
- Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer.PloS one · 2012Article
- Multiple forms of PKR present in the nuclei of acute leukemia cells represent an active kinase that is responsive to stress.Leukemia · 2011Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell division cycle 2 (Cdc2) protein is an essential subunit of M-phase kinase (MPK), which has a key role in G2/M transition. Even though the control of MPK activity has been well established with regard to the phosphorylation of Cdc2 at Thr 14 and/or Tyr 15 and Thr 161, little is known about the proteolytic control of Cdc2. In this study, we observed that Cdc2 was downregulated under genotoxic stresses and that double-stranded RNA-activated protein kinase (PKR) was involved in the process. The PKR-mediated Tyr4 phosphorylation triggered Cdc2 ubiquitination. Phospho-mimic mutations at the Tyr 4 residue (Y4D or Y4E) caused significant ubiquitination of Cdc2 even in the absence of PKR. Our findings demonstrate that (i) PKR, Ser/Thr kinase, phosphorylates its new substrate Cdc2 at the Tyr 4 residue, (ii) PKR-mediated Tyr 4-phosphorylation facilitates Cdc2 ubiquitination and proteosomal degradation, (iii) unphosphorylated Tyr 4 prevents Cdc2 ubiquitination, and (iv) downstream from p53, PKR has a crucial role in G2 arrest and triggers Cdc2 downregulation under genotoxic conditions.
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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.