ArticleMolecular cancer2010
The role of glucocorticoid receptor phosphorylation in Mcl-1 and NOXA gene expression.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- Activating p53Nature communications · 2026Article
- Irisin regulates the phosphorylation of glucocorticoid receptor Ser212 and Ser234 and mediates glucocorticoid-induced muscle atrophy in mice.Communications biology · 2025Article
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- Nuclear Receptors in Bladder Cancer: Insights into miRNA-Mediated Regulation and Potential Therapeutic Implications.International journal of molecular sciences · 2025Review
- The Role of the Glucocorticoid Receptor and Its Phosphorylation in Neurological Disorders.International journal of molecular sciences · 2025Review
- Ciclesonide activates glucocorticoid signaling in neonatal rat lung but does not trigger adverse effects in the cortex and cerebellum.Neurobiology of disease · 2021Article
- The Glucocorticoid Receptor Is a Critical Regulator of HIV Latency in Human Microglial Cells.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Article
- Insight into glucocorticoid receptor signalling through interactome model analysis.PLoS computational biology · 2017Article
- Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia.PloS one · 2017Article
- Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.Oncogene · 2013Article
- Oppositional regulation of Noxa by JNK1 and JNK2 during apoptosis induced by proteasomal inhibitors.PloS one · 2013Article
- Glycogen synthase kinase-3β is involved in ligand-dependent activation of transcription and cellular localization of the glucocorticoid receptor.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Apoptosis induced by overall metabolic stress converges on the Bcl-2 family proteins Noxa and Mcl-1.Apoptosis : an international journal on programmed cell death · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) mediated phosphorylation of glucocorticoid receptor (GR) exerts opposite effects on GR transcriptional activity and affects other posttranslational modifications within this protein. The major phosphorylation site of human GR targeted by MAPK family is the serine 226 and multiple kinase complexes phosphorylate receptor at the serine 211 residue. We hypothesize that GR posttranslational modifications are involved in the determination of the cellular fate in human lymphoblastic leukemia cells. We investigated whether UV signalling through alternative GR phosphorylation determined the cell type specificity of glucocorticoids (GCs) mediated apoptosis.
resultsWe have identified putative Glucocorticoid Response Elements (GREs) within the promoter regulatory regions of the Bcl-2 family members NOXA and Mcl-1 indicating that they are direct GR transcriptional targets. These genes were differentially regulated in CEM-C7-14, CEM-C1-15 and A549 cells by glucocorticoids and JNK pathway. In addition, our results revealed that the S211 phosphorylation was dominant in CEM-C7-14, whereas the opposite was the case in CEM-C1-15 where prevalence of S226 GR phosphorylation was observed. Furthermore, multiple GR isoforms with cell line specific patterns were identified in CEM-C7-14 cells compared to CEM-C1-15 and A549 cell lines with the same antibodies.
conclusionsGR phosphorylation status kinetics, and site specificity as well as isoform variability differ in CEM-C7-14, CEM-C1-15, and A549 cells. The positive or negative response to GCs induced apoptosis in these cell lines is a consequence of the variable equilibrium of NOXA and Mcl-1 gene expression potentially mediated by alternatively phosphorylated GR, as well as the balance of MAPK/CDK pathways controlling GR phosphorylation pattern. Our results provide molecular base and valuable knowledge for improving the GC based therapies of leukaemia.
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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.