ArticleMolecular and cellular biology2004
Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Elevated thymidine kinase 1 expression at baseline predicts poor prognosis in breast cancer patients.Frontiers in oncology · 2026Pooled it
- Trial
- Viral inhibition of the anaphase promoting complex enhances replication by elevating nucleotide pools.PLoS pathogens · 2026Article
- ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.Nature structural & molecular biology · 2025Article
- A comprehensive analysis and experimental validation of TK1 in uterine corpus endometrial carcinoma.Scientific reports · 2024Article
- Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.International journal of molecular sciences · 2023Article
- A monoclonal antibody-based sandwich ELISA for measuring canine Thymidine kinase 1 protein and its role as biomarker in canine lymphoma.Frontiers in veterinary science · 2023Article
- Article
- Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Significant Biomarkers Identification Associated with Cutaneous Squamous Cell Carcinoma Progression.International journal of general medicine · 2022Article
- Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma.BMC molecular and cell biology · 2021Article
- A viral histone-like protein exploits antagonism between linker histones and HMGB proteins to obstruct the cell cycle.Current biology : CB · 2021Article
- Article
- Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker.BMC veterinary research · 2021Article
- Discovery and Validation of a Compound to Target Ewing's Sarcoma.Pharmaceutics · 2021Article
- Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome.Journal of virology · 2021Article
- Thymidine kinase 1 through the ages: a comprehensive review.Cell & bioscience · 2020Review
- Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency.BMC molecular and cell biology · 2020Article
- DCTPP1 prevents a mutator phenotype through the modulation of dCTP, dTTP and dUTP pools.Cellular and molecular life sciences : CMLS · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of human thymidine kinase 1 (hTK1) is highly dependent on the growth states and cell cycle stages in mammalian cells. The amount of hTK1 is significantly increased in the cells during progression to the S and M phases, and becomes barely detectable in the early G(1) phase by a proteolytic control during mitotic exit. This tight regulation is important for providing the correct pool of dTTP for DNA synthesis at the right time in the cell cycle. Here, we investigated the mechanism responsible for mitotic degradation of hTK1. We show that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a necessary but also a rate-limiting factor for mitotic degradation of hTK1. Furthermore, a KEN box sequence located in the C-terminal region of hTK1 is required for its mitotic degradation and interaction capability with Cdh1. By in vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif. Taken together, we concluded that activation of the APC/C-Cdh1 complex during mitotic exit controls timing of hTK1 destruction, thus effectively minimizing dTTP formation from the salvage pathway in the early G(1) phase of the cell cycle in mammalian cells.
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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.