ArticleCell cycle (Georgetown, Tex.)2020
The TLK1/Nek1 axis contributes to mitochondrial integrity and apoptosis prevention via phosphorylation of VDAC1.
Article in Cell cycle (Georgetown, Tex.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Inhibition of LONP1 in prostate cancer: bibliometrics-guided target screening and AI-driven antibody design.International journal of surgery (London, England) · 2026Article
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- The NIMA-related kinase family and cancer.Frontiers in oncology · 2025Review
- Modulation of mitochondrial voltage dependent anion channel: studies on bilayer electrophysiology.Frontiers in physiology · 2025Review
- ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons.Acta neuropathologica communications · 2024Article
- PGK1 can affect the prognosis and development of bladder cancer.Cancer medicine · 2024Article
- TLK1>Nek1 Axis Promotes Nuclear Retention and Activation of YAP with Implications for Castration-Resistant Prostate Cancer.Cancers · 2024Article
- Article
- The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.Cells · 2024Review
- Dissection of Targeting Molecular Mechanisms of Celastrol-induced NephrotoxicityInternational journal of biological sciences · 2024Article
- Article
- Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway.World journal of gastroenterology · 2023Article
- Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023Review
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- The TLK1-MK5 Axis Regulates Motility, Invasion, and Metastasis of Prostate Cancer Cells.Cancers · 2022Article
- TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.Molecular oncology · 2022Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Tousled-like kinase 1: a novel factor with multifaceted role in mCRPC progression and development of therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Pan-Cancer Analysis of Voltage-Dependent Anion Channel (VDAC1) as a Cancer Therapeutic Target or Diagnostic Biomarker.Disease markers · 2022Article
- Interaction of TLK1 and AKTIP as a Potential Regulator of AKT Activation in Castration-Resistant Prostate Cancer Progression.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TLK1/Nek1 axis contributes to cell cycle arrest and implementation of the DDR to mediate survival upon DNA damage. However, when the damage is too severe, the cells typically are forced into apoptosis, and the contribution of TLKs in this process has not been investigated. In contrast, it is known that Nek1 may play a role by phosphorylating VDAC1 maintaining proper opening and closure of the channel and thus mitochondrial integrity. We now show that the activating phosphorylation of Nek1-T141 by TLK1 contributes to the phosphorylation and stability of VDAC1 and thereby to mitochondrial permeability and integrity. Treatment of three different cell lines model that overexpress Nek1-T141A mutant with doxorubicin showed exquisite sensitivity to the drug, with implementation of rapid accumulation of cells with subG1 DNA content (apoptotic) and other alterations in the cell cycle. In addition, these cells displayed reduced oxygen consumption under normal conditions and less reliance on mitochondria and more dependence on glycolysis for energy production. Consistent with greater apoptosis, upon treatment with low doses of doxorubicin, cells overexpressing Nek1-T141A displayed leakage of Cyt-C into the cytoplasmic fraction. This suggests that inhibiting the TLK1/Nek1/VDAC1 nexus could sensitize cancer cells to apoptotic killing in combination with an appropriate DNA damaging agent. We in fact have previously reported that Nek1 expression is elevated in advanced Prostate Cancer (PCa) and we now report that VDAC1 expression is elevated and correlated with disease stage, thereby making the TLK1/Nek1/VDAC1 nexus a very attractive target for PCa.
Indexed as
Identifiers
What OpenQuestion holds
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.