ArticleMolecular and cellular biology2010
Cdk2 and Cdk4 regulate the centrosome cycle and are critical mediators of centrosome amplification in p53-null cells.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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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.
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Who cites it
61 citing papers in PubMed, 93 citations in OpenAlex.
- New 4-Benzenesulfonamide Derivatives of Pyrazolo[1,5-a][1,3,5] triazine as Purine Bioisosteres: Development, Synthesis, and Anticancer Perspective.Current medicinal chemistry · 2026Article
- 14-3-3ε inhibits premature centriole disengagement by inhibiting the activity of Plk1 and separase.Journal of cell science · 2025Article
- Cell cycle proteins: Linking the cell cycle to tumors.Oncology research · 2025Review
- Mitotic kinases are emerging therapeutic targets against metastatic breast cancer.Cell division · 2024Review
- Overexpression of SMYD3 Promotes Autosomal Dominant Polycystic Kidney Disease by Mediating Cell Proliferation and Genome Instability.Biomedicines · 2024Article
- Centrosome amplification-related signature correlated with immune microenvironment and treatment response predicts prognosis and improves diagnosis of hepatocellular carcinoma by integrating machine learning and single-cell analyses.Hepatology international · 2024Article
- CDK2 inhibition disorders centrosome stoichiometry and alters cellular outcomes in aneuploid cancer cells.Cancer biology & therapy · 2023Article
- Cigarette smoke condensate induces centrosome clustering in normal lung epithelial cells.Cancer medicine · 2023Article
- Ethnic and racial-specific differences in levels of centrosome-associated mitotic kinases, proliferative and epithelial-to-mesenchymal markers in breast cancers.Cell division · 2022Article
- Keep Calm and Carry on with Extra Centrosomes.Cancers · 2022Review
- CDK4 has the ability to regulate Aurora B and Cenpp expression in mouse keratinocytes.Oncology letters · 2021Article
- The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells.Scientific reports · 2021Article
- Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.Biomedicines · 2021Review
- Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies.Cancer metastasis reviews · 2021Review
- Loss of Both CDKN2A and CDKN2B Allows for Centrosome Overduplication in Melanoma.The Journal of investigative dermatology · 2020Article
- Role of E2Fs and mitotic regulators controlled by E2Fs in the epithelial to mesenchymal transition.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Targeting centrosome amplification, an Achilles' heel of cancer.Biochemical Society transactions · 2019Review
- Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth.Cancers · 2019Article
- MYCN is amplified during S phase, and c‑myb is involved in controlling MYCN expression and amplification in MYCN‑amplified neuroblastoma cell lines.Molecular medicine reports · 2019Article
- Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia.Journal of cellular and molecular medicine · 2018Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The two mitotic centrosomes direct spindle bipolarity to maintain euploidy. Centrosome amplification-the acquisition of > or =3 centrosomes-generates multipolar mitoses, aneuploidy, and chromosome instability to promote cancer biogenesis. While much evidence suggests that Cdk2 is the major conductor of the centrosome cycle and that it mediates centrosome amplification induced by various altered tumor suppressors, the role played by Cdk4 in a normal or deregulated centrosome cycle is unknown. Using a gene knockout approach, we report that Cdk2 and Cdk4 are critical to the centrosome cycle, since centrosome separation and duplication are premature in Cdk2(-)(/)(-) mouse embryonic fibroblasts (MEFs) and are compromised in Cdk4(-)(/)(-) MEFs. Additionally, ablation of Cdk4 or Cdk2 abrogates centrosome amplification and chromosome instability in p53-null MEFs. Absence of Cdk2 or Cdk4 prevents centrosome amplification by abrogating excessive centriole duplication. Furthermore, hyperactive Cdk2 and Cdk4 deregulate the licensing of the centrosome duplication cycle in p53-null cells by hyperphosphorylating nucleophosmin (NPM) at Thr199, as evidenced by observations that ablation of Cdk2, Cdk4, or both Cdk2 and Cdk4 abrogates that excessive phosphorylation. Since a mutant form of NPM lacking the G(1) Cdk phosphorylation site (NPM(T199A)) prevents centrosome amplification to the same extent as ablation of Cdk2 or Cdk4, we conclude that the Cdk2/Cdk4/NPM pathway is a major guardian of centrosome dysfunction and genomic integrity.
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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.