ArticleThe EMBO journal2017
Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.The Biochemical journal · 2026Article
- Atypical cell cycle regulation over neural stem cell expansion.Stem cell reports · 2026Article
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Slower CDK4 and faster CDK2 activation in the cell cycle.Structure (London, England : 1993) · 2024Article
- Atypical cell cycle regulation promotes mammary stem cell expansion during mammary development and tumourigenesis.Breast cancer research : BCR · 2024Article
- Identification and validation of aging-related genes in heart failure based on multiple machine learning algorithms.Frontiers in immunology · 2024Article
- Development of allosteric and selective CDK2 inhibitors for contraception with negative cooperativity to cyclin binding.Nature communications · 2023Article
- The atypical CDK activator RingoA/Spy1 regulates exit from quiescence in neural stem cells.iScience · 2023Article
- Emerging approaches to CDK inhibitor development, a structural perspective.RSC chemical biology · 2023Article
- SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1.Cell death and differentiation · 2023Article
- Stabilization of c-Myc by the atypical cell cycle regulator, Spy1, decreases efficacy of breast cancer treatments.Breast cancer research and treatment · 2022Article
- Short Linear Motifs Orchestrate Functioning of Human Proteins during Embryonic Development, Redox Regulation, and Cancer.Metabolites · 2022Article
- Machine learning to estimate the local quality of protein crystal structures.Scientific reports · 2021Article
- Gene Expression Profile and Co-Expression Network of Pearl Gentian Grouper under Cold Stress by Integrating Illumina and PacBio Sequences.Animals : an open access journal from MDPI · 2021Article
- The SUN1-SPDYA interaction plays an essential role in meiosis prophase I.Nature communications · 2021Article
- Ubiquitin-proteasome system-targeted therapy for uveal melanoma: what is the evidence?Acta pharmacologica Sinica · 2021Review
- Structural basis for CDK7 activation by MAT1 and Cyclin H.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review of rationale and progress toward targeting cyclin-dependent kinase 2 (CDK2) for male contraception†.Biology of reproduction · 2020Review
- Common Functions of Disordered Proteins across Evolutionary Distant Organisms.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. Spy1/RINGO (Spy1) proteins bind and activate Cdk but are resistant to canonical regulatory mechanisms that establish cell-cycle checkpoints. Cancer cells exploit Spy1 to stimulate proliferation through inappropriate activation of Cdks, yet the mechanism is unknown. We have determined crystal structures of the Cdk2-Spy1 and p27-Cdk2-Spy1 complexes that reveal how Spy1 activates Cdk. We find that Spy1 confers structural changes to Cdk2 that obviate the requirement of Cdk activation loop phosphorylation. Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. We identify mutations in Spy1 that ablate its ability to activate Cdk2 and to proliferate cells. Our structural description of Spy1 provides important mechanistic insights that may be utilized for targeting upregulated Spy1 in cancer.
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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.