ArticleScientific reports2015
Structures of the CDK12/CycK complex with AMP-PNP reveal a flexible C-terminal kinase extension important for ATP binding.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature.Clinical epigenetics · 2025Article
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- Structure-independent machine-learning predictions of the CDK12 interactome.Biophysical journal · 2024Article
- Research progress of anticancer drugs targeting CDK12.RSC medicinal chemistry · 2023Review
- Article
- Structure and activation mechanism of the yeast RNA Pol II CTD kinase CTDK-1 complex.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation.eLife · 2020Article
- A Functional Kinase Is Necessary for Cyclin-Dependent Kinase G1 (CDKG1) to Maintain Fertility at High Ambient Temperature inFrontiers in plant science · 2020Article
- Pan-Cancer Analysis ofThe oncologist · 2019Article
- Human CDK12 and CDK13, multi-tasking CTD kinases for the new millenium.Transcription · 2019Review
- CDK12: an emerging therapeutic target for cancer.Journal of clinical pathology · 2018Review
- Structural insights into the functional diversity of the CDK-cyclin family.Open biology · 2018Review
- Structure-based discovery of cyclin-dependent protein kinase inhibitors.Essays in biochemistry · 2017Review
- CDK12 regulates alternative last exon mRNA splicing and promotes breast cancer cell invasion.Nucleic acids research · 2017Article
- Identification and analysis of mutational hotspots in oncogenes and tumour suppressors.Oncotarget · 2017Article
- Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response.Cold Spring Harbor molecular case studies · 2016Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinase 12 (CDK12) promotes transcriptional elongation by phosphorylation of the RNA polymerase II C-terminal domain (CTD). Structure-function studies show that this activity is dependent on a C-terminal kinase extension, as well as the binding of cyclin K (CycK). To better define these interactions we determined the crystal structure of the human CDK12/CycK complex with and without the kinase extension in the presence of AMP-PNP. The structures revealed novel features for a CDK, including a large β4-β5 loop insertion that contributes to the N-lobe interaction with the cyclin. We also observed two different conformations of the C-terminal kinase extension that effectively open and close the ATP pocket. Most notably, bound AMP-PNP was only observed when trapped in the closed state. Truncation of this C-terminal structure also diminished AMP-PNP binding, as well as the catalytic activity of the CDK12/CycK complex. Further kinetic measurements showed that the full length CDK12/CycK complex was significantly more active than the two crystallised constructs suggesting a critical role for additional domains. Overall, these results demonstrate the intrinsic flexibility of the C-terminal extension in CDK12 and highlight its importance for both ATP binding and kinase activity.
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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.