Evidence map›Paper›PMID 23907123›Full record

ArticleCell cycle (Georgetown, Tex.)2013

The p27-Skp2 axis mediates glucocorticoid-induced cell cycle arrest in T-lymphoma cells.

Michael K Kullmann, Claudia Grubbauer, Katrin Goetsch, Heidelinde Jäkel, Silvio R Podmirseg, Alexander Trockenbacher, Christian Ploner, Andrew C B Cato, Carsten Weiss, Reinhard Kofler and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  3. Review
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  5. Article
  6. [Targeting Cullin-RING E3 ligases for anti-cancer therapy: efforts on drug discovery].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020
    Review
  7. Article
  8. Stabilization of p27FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  9. Article
  10. A patent review of the ubiquitin ligase system: 2015-2018.Expert opinion on therapeutic patents · 2018
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Michael K KullmannDivision of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. michael.kullmann@i-med.ac.at
Claudia Grubbauer
Katrin Goetsch
Heidelinde Jäkel
Silvio R Podmirseg
Alexander Trockenbacher
Christian Ploner
Andrew C B Cato
Carsten Weiss
Reinhard Kofler
Ludger Hengst
Innsbruck Medical University · ATKarlsruhe Institute of Technology · DETyrolean Cancer Research Institute · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucocorticoid therapy is an important treatment modality of hematological malignancies, especially T-cell acute lymphoblastic leukemia (T-ALL). Glucocorticoids are known to induce a cell cycle arrest and apoptosis in T-lymphoma cells. We could demonstrate that the cell cycle arrest induced by the synthetic glucocorticoid dexamethasone (Dex) clearly precedes apoptosis in human CEM T-ALL and murine S49.1 T-lymphoma cells. Cyclin D3 is strongly downregulated, whereas the CDK inhibitor p27 (Kip1) (p27) is strongly upregulated in response to dexamethasone in these cells. RNAi-mediated knockdown of p27 as well as overexpression of its negative regulator Skp2 revealed the critical function of p27 in the Dex-induced G 1 arrest of CEM cells. Our studies indicate that several mechanisms contribute to the increase of p27 protein in our T-lymphoma cell lines. We found a significant upregulation of p27 mRNA in S49.1 and CEM cells. In addition, Dex treatment activated the mouse p27 promotor in reporter gene experiments, indicating a transcriptional regulation. However, the relatively moderate induction of p27 mRNA levels by Dex did not explain the strong increase of p27 protein in CEM and S49.1 cells. We found clear evidence for a posttranslational mechanism responsible for the robust increase in p27 protein. Dex treatment of S49.1 and CEM cells increases the half-life of p27 protein, which indicates that decreased protein degradation is the primary mechanism of p27 induction by glucocorticoids. Interestingly, we found that Dex treatment decreased the protein and mRNA levels of the negative regulator of p27 protein and E3 ubiquitin ligase subunit Skp2. We conclude that the cell cycle inhibitor p27 and its negative regulator Skp2 are key players in the glucocorticoid-induced growth suppression of T-lymphoma cells and should be considered as potential drug targets to improve therapies of T-cell malignancies.

Indexed as

AnimalsApoptosisBlotting, WesternCell Cycle CheckpointsCell Line, TumorCyclin D3Cyclin-Dependent Kinase Inhibitor p27DexamethasoneDNA PrimersGene Expression RegulationGlucocorticoidsHalf-LifeHumansImmunoblottingLuciferasesMiceCyclin D3Cyclin-Dependent Kinase Inhibitor p27DexamethasoneDNA PrimersGlucocorticoidsLuciferasesS-Phase Kinase-Associated Proteinscell cycle controldexamethasoneglucocorticoidlymphomap27Kip1proliferationSkp2T-ALL

Identifiers

PMID23907123
PMCPMC3865052
OpenAlexW1988837447

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Registered trials

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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.