ArticleAmerican journal of physiology. Renal physiology2011
Cdk2-dependent phosphorylation of p21 regulates the role of Cdk2 in cisplatin cytotoxicity.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 35 citations in OpenAlex.
- IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.Nature communications · 2026Article
- CCN2 Activates Cellular Senescence Leading to Kidney Fibrosis in Folic Acid-Induced Experimental Nephropathy.International journal of molecular sciences · 2025Article
- Mechanistic insights into chemotherapy-induced circadian disruption using rodent models.Trends in neurosciences · 2025Review
- p21Cancers · 2024Article
- Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair.Journal of cellular and molecular medicine · 2024Article
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- PFKFB3 mediates tubular cell death in cisplatin nephrotoxicity by activating CDK4.Translational research : the journal of laboratory and clinical medicine · 2023Article
- Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes.Frontiers in pharmacology · 2021Article
- Article
- Negative feedback by conserved kinases patterns the degradation ofDevelopment (Cambridge, England) · 2020Article
- Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.American journal of physiology. Renal physiology · 2018Article
- The cell cycle biomarkers: promising research, but do not oversell them.Clinical kidney journal · 2016Review
- DNA damage response in cisplatin-induced nephrotoxicity.Archives of toxicology · 2015Review
- Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI.Journal of the American Society of Nephrology : JASN · 2015Observational
- CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.The Journal of biological chemistry · 2015Article
- Cell cycle arrest in a model of colistin nephrotoxicity.Physiological genomics · 2013Article
- Assembly, activation, and substrate specificity of cyclin D1/Cdk2 complexes.Biochemistry · 2013Article
- Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak.Cell death discoveryArticle
- Mimicking Cdk2 phosphorylation of Bcl-xL at Ser73 results in caspase activation and Bcl-xL cleavage.Cell death discoveryArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cisplatin cytotoxicity is dependent on cyclin-dependent kinase 2 (Cdk2) activity in vivo and in vitro. We found that an 18-kDa protein identified by mass spectrometry as p21(WAF1/Cip1) was phosphorylated by Cdk2 starting 12 h after cisplatin exposure. The analysis showed it was phosphorylated at serine 78, a site not previously identified. The adenoviral transduction of p21 before cisplatin exposure protects from cytotoxicity by inhibiting Cdk2. Although cisplatin causes induction of endogenous p21, the protection is inefficient. We hypothesized that phosphorylation of p21 at serine 78 could affect its role as a Cdk inhibitor, and thereby lessen its ability to protect from cisplatin cytotoxicity. To investigate the effect of serine 78 phosphorylation on p21 activity, we replaced serine 78 with aspartic acid, creating the phosphomimic p21(S78D). Mutant p21(S78D) was an inefficient inhibitor of Cdk2 and was inefficient at protecting TKPTS cells from cisplatin-induced cell death. We conclude that phosphorylation of p21 by Cdk2 limits the effectiveness of p21 to inhibit Cdk2, which is the mechanism for continued cisplatin cytotoxicity even after the induction of a protective protein.
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.