ArticleCell death & disease2012
Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Translational control of AMPK activity in melanoma.Cell communication and signaling : CCS · 2026Article
- MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress.EXCLI journal · 2021Article
- Mechanism of inositol-requiring enzyme 1-alpha inhibition in endoplasmic reticulum stress and apoptosis in ovarian cancer cells.Journal of cell communication and signaling · 2020Article
- Tau-induced upregulation of C/EBPβ-TRPC1-SOCE signaling aggravates tauopathies: A vicious cycle in Alzheimer neurodegeneration.Aging cell · 2020Article
- Endoplasmic reticulum stress induces liver cells apoptosis after brain death by suppressing the phosphorylation of protein phosphatase 2A.Molecular medicine reports · 2020Article
- Novel roles of ER stress in repressing neural activity and seizures through Mdm2- and p53-dependent protein translation.PLoS genetics · 2019Article
- Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- ACTN4 regulates the stability of RIPK1 in melanoma.Oncogene · 2018Article
- RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.Cell death & disease · 2018Article
- MAP4K4 is a novel MAPK/ERK pathway regulator required for lung adenocarcinoma maintenance.Molecular oncology · 2017Article
- RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy.Autophagy · 2015Article
- Noxa upregulation by oncogenic activation of MEK/ERK through CREB promotes autophagy in human melanoma cells.Oncotarget · 2014Article
- 67-kDa laminin receptor-dependent protein phosphatase 2A (PP2A) activation elicits melanoma-specific antitumor activity overcoming drug resistance.The Journal of biological chemistry · 2014Article
- Induction of endoplasmic reticulum stress as a strategy for melanoma therapy: is there a future?Melanoma management · 2014Review
- Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II.The Journal of cell biology · 2014Article
- Oncogenic suppression of PHLPP1 in human melanoma.Oncogene · 2014Article
- Oncogenic activation of MEK/ERK primes melanoma cells for adaptation to endoplasmic reticulum stress.The Journal of investigative dermatology · 2014Article
- Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway.Drug design, development and therapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress triggers apoptosis by activating Bim in diverse types of cells, which involves dephosphorylation of Bim(EL) by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that ER stress reduces PP2A activity leading to increased ERK activation and subsequent phosphorylation and proteasomal degradation of Bim(EL). Despite sustained upregulation of Bim at the transcriptional level, the Bim(EL) protein expression was downregulated after an initial increase in melanoma cells subjected to pharmacological ER stress. This was mediated by increased activity of ERK, whereas the phosphatase activity of PP2A was reduced by ER stress in melanoma cells. The increase in ERK activation was, at least in part, due to reduced dephosphorylation by PP2A, which was associated with downregulation of the PP2A catalytic C subunit. Notably, instead of direct dephosphorylation of Bim(EL), PP2A inhibited its phosphorylation indirectly through dephosphorylation of ERK in melanoma cells. Taken together, these results identify downregualtion of PP2A activity as an important protective mechanism of melanoma cells against ER stress-induced apoptosis.
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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.