ArticleThe EMBO journal2001
T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and regulates its CTD kinase activity.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 133 citations in OpenAlex.
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Emerging roles of cyclin-dependent kinase 7 in health and diseases.Trends in molecular medicine · 2025Review
- Review
- Structural basis of Cdk7 activation by dual T-loop phosphorylation.Nature communications · 2024Article
- Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy.Cardiovascular research · 2024Article
- Structural basis of Cdk7 activation by dual T-loop phosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups.Biomolecules · 2022Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- Post-translational Modifications of Serine/Threonine and Histidine Kinases and Their Roles in Signal Transductions in Synechocystis Sp. PCC 6803.Applied biochemistry and biotechnology · 2021Review
- CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreatitis.PLoS pathogens · 2021Article
- Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer.Computational and mathematical methods in medicine · 2021Article
- Structural basis for CDK7 activation by MAT1 and Cyclin H.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The cryoelectron microscopy structure of the human CDK-activating kinase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CDK7 inhibitors as anticancer drugs.Cancer metastasis reviews · 2020Review
- Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer.Cancer cell international · 2020Article
- CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus.Genes & development · 2020Article
- A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.Nature communications · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cyclin-dependent kinase (CDK)7-cyclin H, the CDK-activating kinase (CAK) and TFIIH-associated kinase in metazoans can be activated in vitro through T-loop phosphorylation or binding to the RING finger protein MAT1. Although the two mechanisms can operate independently, we show that in a physiological setting, MAT1 binding and T-loop phosphorylation cooperate to stabilize the CAK complex of Drosophila. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop. Mutation of both phosphorylation sites causes temperature-dependent dissociation of CDK7 complexes and lethality. Furthermore, phosphorylation of Thr170 greatly stimulates the activity of the CDK7- cyclin H-MAT1 complex towards the C-terminal domain of RNA polymerase II without significantly affecting activity towards CDK2. Remarkably, the substrate-specific increase in activity caused by T-loop phosphorylation is due entirely to accelerated enzyme turnover. Thus phosphorylation on Thr170 could provide a mechanism to augment CTD phosphorylation by TFIIH-associated CDK7, and thereby regulate transcription.
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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.