ArticleMolecular and cellular biology2014
Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- WITHDRAWN: From CDK4/6 to CDK2 and KAT: Evolving therapeutic approaches in HR+/HER2- breast cancer.Breast (Edinburgh, Scotland) · 2026Article
- Suppression of neuronal p27 impairs cognitive function in middle-aged mice.Neurobiology of disease · 2026Article
- Stabilization of cyclin D3 protein by CDKN1A (p21Cell communication and signaling : CCS · 2026Article
- Review
- Transcription factor YY1 adversely governs ovarian granulosa cell growth in PCOS by transcription activation-mediated CDKN1C upregulation.Functional & integrative genomics · 2024Article
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Disruption of Toxoplasma gondii-Induced Host Cell DNA Replication Is Dependent on Contact Inhibition and Host Cell Type.mSphere · 2022Article
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- A curious case of cyclin-dependent kinases in neutrophils.Journal of leukocyte biology · 2022Review
- Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer.Breast cancer research : BCR · 2022Review
- Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies.Frontiers in nutrition · 2022Review
- The evolution of cyclin dependent kinase inhibitors in the treatment of cancer.Expert review of anticancer therapy · 2021Review
- Insight into Bortezomib Focusing on Its Efficacy against P-gp-Positive MDR Leukemia Cells.International journal of molecular sciences · 2021Article
- Endothelial sprouting, proliferation, or senescence: tipping the balance from physiology to pathology.Cellular and molecular life sciences : CMLS · 2021Review
- A unified model for the G1/S cell cycle transition.Nucleic acids research · 2020Review
- Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27.Scientific reports · 2019Article
- Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.Cell death & disease · 2019Article
- Divide or Commit - Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis.Frontiers in cell and developmental biology · 2019Review
- Article
- Proliferation of hippocampal progenitors relies on p27-dependent regulation of Cdk6 kinase activity.Cellular and molecular life sciences : CMLS · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The Cip/Kip family, namely, p21(Cip1), p27(Kip1), and p57(Kip2), are stoichiometric cyclin-dependent kinase inhibitors (CKIs). Paradoxically, they have been proposed to also act as positive regulators of Cdk4/6-cyclin D by stabilizing these heterodimers. Loss of p21(Cip1) and p27(Kip1) reduces Cdk4/6-cyclin D complexes, although with limited phenotypic consequences compared to the embryonic lethality of Cdk4/6 or triple cyclin D deficiency. This milder phenotype was attributed to Cdk2 compensatory mechanisms. To address this controversy using a genetic approach, we generated Cdk2(-/-) p21(-/-) p27(-/-) mice. Triple-knockout mouse embryonic fibroblasts (MEFs) displayed minimal levels of D-type cyclins and Cdk4/6-cyclin D complexes. p57(Kip2) downregulation in the absence of p21(Cip1) and p27(Kip1) aggravated this phenotype, yet MEFs lacking all Cip/Kip proteins exhibited increased retinoblastoma phosphorylation, together with enhanced proliferation and transformation capacity. In vivo, Cdk2 ablation induced partial perinatal lethality in p21(-/-) p27(-/-) mice, suggesting partial Cdk2-dependent compensation. However, Cdk2(-/-) p21(-/-) p27(-/-) survivors displayed all phenotypes described for p27(-/-) mice, including organomegalia and pituitary tumors. Thus, Cip/Kip deficiency does not impair interphasic Cdk activity even in the absence of Cdk2, suggesting that their Cdk-cyclin assembly function is dispensable for homeostatic control in most cell types.
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