Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration
Open accessAbstract
Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.
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Cdk1 or Pten were used as controls with predictable influences on cancer.
“Cdk1 or Pten were used as controls with predictable influences on cancer (36, 37).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [36]
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“The mammalian genome contains at least 20 different Cdks, and widespread compensation among Cdks and cyclins has been reported (2, 3).”
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The Polyploid State Plays a Tumor-Suppressive Role in the Liver
Zhang, S., Zhou, K., Luo, X., Li, L., Tu, H.-C., Sehgal, A., Nguyen, L. H., Zhang, Y., Gopal, P., Tarlow, B. D., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.010 · Cited by 180 · see citing works
Loss of Cdk2 and cyclin A2 impairs cell proliferation and tumorigenesis.
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The origin of hepatocellular carcinoma depends on metabolic zonation
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- Authors
- Diril, M. K., Ratnacaram, C. K., Padmakumar, V. C., Du, T., Wasser, M., Coppola, V., Tessarollo, L., & Kaldis, P.
- Affiliations
- Agency for Science, Technology and Research (SG)
- National Cancer Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-02-21
- Volume
- 109
- Issue
- 10
- Pages
- 3826-3831
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3309725
- OpenAlex
- W2079019214
- Cited by
- 385
- References
- 2
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 35 · 2023: 33 · 2022: 35 · 2021: 31 · 2020: 47 · 2019: 33 · 2018: 27 · 2017: 22 · 2016: 19 · 2015: 22 · 2014: 16 · 2013: 15 · 2012: 7
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- cyclin-dependent kinase 1, CDK1, cell division, DNA re-replication, liver regeneration, conditional knockout mice, embryonic development, S phase progression
- MeSH terms
- Animals, Blastocyst, Cell Cycle, Cell Division, DNA Replication, Liver Regeneration, Mitosis, Polyploidy, Genes, ras, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, S Phase, CDC2 Protein Kinase, Mice, Knockout, ras Proteins, Gene Silencing, Mice
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