ArticleOncogene2004
ERK1/2 and p38 cooperate to induce a p21CIP1-dependent G1 cell cycle arrest.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer.Molecular carcinogenesis · 2018Pooled it
- Article
- EZH2 inhibition induces senescence via ERK1/2 signaling pathway in multiple myeloma.Acta biochimica et biophysica Sinica · 2024Article
- Cip1 tunes cell cycle arrest duration upon calcineurin activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The mechanism of activation of MEK1 by B-Raf and KSR1.Cellular and molecular life sciences : CMLS · 2022Article
- Methyl Donors Reduce Cell Proliferation by Diminishing Erk-Signaling and NFkB Levels, While Increasing E-Cadherin Expression in Panc-1 Cell Line.International journal of molecular sciences · 2022Article
- Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….Biochemical Society transactions · 2020Review
- 12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway.International journal of molecular sciences · 2020Article
- Senescent T cells within suppressive tumor microenvironments: emerging target for tumor immunotherapy.The Journal of clinical investigation · 2020Review
- Article
- Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling.International journal of molecular sciences · 2019Article
- Mechanisms shaping the role of ERK1/2 in cellular senescence (Review).Molecular medicine reports · 2019Review
- Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence.Oncotarget · 2018Article
- SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex.Molecular cancer · 2018Article
- TMIGD1 acts as a tumor suppressor through regulation of p21Cip1/p27Kip1 in renal cancer.Oncotarget · 2018Article
- Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4.Nature communications · 2017Article
- Article
- Identification of DYRK1B as a substrate of ERK1/2 and characterisation of the kinase activity of DYRK1B mutants from cancer and metabolic syndrome.Cellular and molecular life sciences : CMLS · 2016Article
- Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53.Cell cycle (Georgetown, Tex.) · 2016Article
- MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road.Nature reviews. Cancer · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
To study the mechanisms by which mitogen- and stress-activated protein kinases regulate cell cycle re-entry, we have used a panel of conditional kinases that stimulate defined MAPK or SAPK cascades. Activation of DeltaMEKK3:ER* during serum restimulation of quiescent cells causes a strong activation of JNK1 and p38alpha but only a modest potentiation of serum-stimulated ERK1/2 activity. In CCl39 cells this promoted a sustained G1 arrest that correlated with decreased expression of cyclin D1 and Cdc25A, increased expression of p21CIP1 and inhibition of CDK2 activity. In Rat-1 cells, in which p21(CIP1) expression is silenced by methylation, DeltaMEKK3:ER* activation caused only a transient delay in the S phase entry rather than a sustained G1 arrest. Furthermore, p21CIP1-/- 3T3 cells were defective for the DeltaMEKK3:ER*-induced G1 cell cycle arrest compared to their wild-type counterparts. These results suggest that activated DeltaMEKK3:ER* inhibits the G1 --> S progression by two kinetically distinct mechanisms, with expression of p21CIP1 being required to ensure a sustained G1 cell cycle arrest. The ERK1/2 and p38alphabeta pathways cooperated to induce p21CIP1 expression and inhibition of p38alphabeta caused a partial reversal of the cell cycle arrest. In contrast, selective activation of ERK1/2 by DeltaRaf-1:ER* did not inhibit serum stimulated cell cycle re-entry. Finally, selective activation of JNK by DeltaMEKK1:ER* failed to inhibit cell cycle re-entry, even in cells that retained wild-type p53, arguing against a major role for JNK alone in antagonizing the G1 --> S transition.
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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.