ArticleMolecular cancer therapeutics2015
Specific CP110 Phosphorylation Sites Mediate Anaphase Catastrophe after CDK2 Inhibition: Evidence for Cooperation with USP33 Knockdown.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 21 citations in OpenAlex.
- The Centriole Biogenesis Cycle: Temporal Mechanisms, Autonomy and Coupling to the Cell Cycle and Other Cellular Clocks.Advances in experimental medicine and biology · 2026Review
- CDK2 inhibition disorders centrosome stoichiometry and alters cellular outcomes in aneuploid cancer cells.Cancer biology & therapy · 2023Article
- Whole-Genome Duplication and Genome Instability in Cancer Cells: Double the Trouble.International journal of molecular sciences · 2023Review
- Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review.International journal of molecular sciences · 2021Review
- A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers.Molecular cancer therapeutics · 2021Article
- Drug-Target Interaction Prediction Based on Adversarial Bayesian Personalized Ranking.BioMed research international · 2021Article
- Ciliogenesis and Hedgehog signalling are suppressed downstream of KRAS during acinar-ductal metaplasia in mouse.Disease models & mechanisms · 2020Article
- TRIGGERING ANAPHASE CATASTROPHE TO COMBAT ANEUPLOID CANCERS.Transactions of the American Clinical and Climatological Association · 2020Article
- Targeting centrosome amplification, an Achilles' heel of cancer.Biochemical Society transactions · 2019Review
- Engaging Anaphase Catastrophe Mechanisms to Eradicate Aneuploid Cancers.Molecular cancer therapeutics · 2018Review
- Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulation of the cell cycle and centrosome biology by deubiquitylases.Biochemical Society transactions · 2017Review
- Next-Generation CDK2/9 Inhibitors and Anaphase Catastrophe in Lung Cancer.Journal of the National Cancer Institute · 2017Article
- Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2.Molecular cancer therapeutics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Chromosomal instability (CIN) is a hallmark of solid tumor biology and is implicated in carcinogenesis. Preferentially eliminating malignant cells by targeting CIN and aneuploidy is an attractive antineoplastic strategy. We previously reported that CDK2 antagonism causes lung cancer cells to undergo anaphase catastrophe and apoptosis through inhibition of phosphorylation of the centrosomal protein CP110. Cells with activating KRAS mutations were particularly sensitive to CDK2 inhibition due to downregulation of CP110 protein levels. This study investigated mechanisms of CDK2 antagonism that mediate anaphase catastrophe via changes in CP110 protein expression and how activated KRAS affects CP110 levels in lung cancers. Site-directed mutagenesis revealed candidate CDK phosphorylation sites of CP110 (residues Ser 170 and Thr 194) critical for conferring anaphase catastrophe by altering centrosome clustering in mitosis. Intriguingly, KRAS mutation can promote CP110 protein degradation by upregulating the ubiquitin ligase SCF(cyclinF), which targets CP110 protein for destabilization. Finally, CDK2 inhibitor response was enhanced when combined with knockdown of the deubiquitinase USP33 that in turn accelerates CP110 protein degradation. Thus, this study provides molecular pharmacologic insights into how CP110 expression regulates response to CDK2 inhibition. An improved understanding of in vitro antineoplastic mechanisms of combining CDK2 antagonism with induced CP110 repression provides a rationale for exploring clinical consequences of this strategy. Taken together, preclinical findings obtained from combining CDK2 inhibition with USP33 repression have implications for treating patients with non-small cell lung cancers.
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.