MiR-221/222 suppression induced by activation of the cAMP/PKA/CREB1 pathway is required for cAMP-induced bidirectional differentiation of glioma cells.
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ABSTRACT:
PROVIDER: PRJNA756194 | ENA |
REPOSITORIES: ENA
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Project description:Factors that increase cAMP levels can induce lineage-specific differentiation of glioma cells into astrocyte-like cells. However, the differentiation pattern and underlying mechanisms remain unclear. Here, we find that cAMP/PKA/CREB1-induced miR-221/222 suppression contributes to the neuron-like differentiation of gliomas. cAMP agonists selectively induced neuron- and astrocyte-like but not oligodendrocyte-like differentiation of C6 glioma cells. PKA inhibitors and CREB1 knockout blocked neuron-like differentiation of glioma cells. cAMP inhibited miR-221/222 in a PKA/CREB1 dependent manner. Importantly, both in vitro and in vivo assays demonstrated that transcriptional suppression of miR-221/222 is required for neuronal differentiation of glioma cells. Our findings suggest that increasing cAMP levels can induce bidirectional differentiation of glioma cells. Furthermore, the miR-221/222 cluster acts as an epigenetic brake during glioma differentiation. Factors that increase cAMP levels can induce lineage-specific differentiation of glioma cells into astrocyte-like cells. However, the differentiation pattern and underlying mechanisms remain unclear. Here, we find that cAMP/PKA/CREB1-induced miR-221/222 suppression contributes to the neuron-like differentiation of gliomas. cAMP agonists selectively induced neuron- and astrocyte-like but not oligodendrocyte-like differentiation of C6 glioma cells. PKA inhibitors and CREB1 knockout blocked neuron-like differentiation of glioma cells. cAMP inhibited miR-221/222 in a PKA/CREB1 dependent manner. Importantly, both in vitro and in vivo assays demonstrated that transcriptional suppression of miR-221/222 is required for neuronal differentiation of glioma cells. Our findings suggest that increasing cAMP levels can induce bidirectional differentiation of glioma cells. Furthermore, the miR-221/222 cluster acts as an epigenetic brake during glioma differentiation.
2021-08-24 | GSE182498 | GEO
Project description:Factors that increase cAMP levels can induce lineage-specific differentiation of glioma cells into astrocyte-like cells. However, the differentiation pattern and underlying mechanisms remain unclear. Here, we find that cAMP/PKA/CREB1-induced miR-221/222 suppression contributes to the neuron-like differentiation of gliomas. cAMP agonists selectively induced neuron- and astrocyte-like but not oligodendrocyte-like differentiation of C6 glioma cells. PKA inhibitors and CREB1 knockout blocked neuron-like differentiation of glioma cells. cAMP inhibited miR-221/222 in a PKA/CREB1 dependent manner. Importantly, both in vitro and in vivo assays demonstrated that transcriptional suppression of miR-221/222 is required for neuronal differentiation of glioma cells. Our findings suggest that increasing cAMP levels can induce bidirectional differentiation of glioma cells. Furthermore, the miR-221/222 cluster acts as an epigenetic brake during glioma differentiation.
2024-08-20 | GSE182413 | GEO
Project description:MiR-221/222 suppression induced by activation of the cAMP/PKA/CREB1 pathway is required for cAMP-induced bidirectional differentiation of glioma cells [miRNA]
| PRJNA756519 | ENA
Project description:This data provides evidence that elevation of cAMP levels has a dramatic effect on the transcriptome of yeast cells, with particular emphasis on mitochondrial function and the promotion of ROS production S. cerevisiae cells lacking the high affinity phosphodiesterase PDE2or both PDE2 and the PKA subunit TPK3 were grown for 24h in rich media in the presence of 4mM exogensously added cAMP. 8 samples.
2010-11-24 | E-GEOD-25541 | biostudies-arrayexpress
Project description:Cyclic AMP activates two downstream factors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC) and both downstream signalings induce syncytialization, cell fusion and the production of hCG and progesterone. We used microarray to identify novel transcription factors related to syncytialization in two cAMP signaling-stimulated BeWo cells.
2017-09-30 | GSE100095 | GEO
Project description:Vasopressin/cAMP/protein kinase A (PKA)/aquaporin-2 (AQP2) water channels signaling in the kidneys is a canonical pathway that determines AQP2 activity in response to body fluid balance. AQP2 phosphorylation by PKA increases water reabsorption from urine for the prevention of further water loss. We used several activators of cAMP/PKA signaling as screening tools to generate various phosphorylation patterns of PKA substrates and AQP2 in a mouse cortical collecting duct principal cell line (mpkCCDcl4). We next quantified phosphorylation levels of PKA substrates and AQP2 after western blot analysis using a phospho-PKA substrates antibody. Finally, we screen for PKA substrates whose phosphorylation levels were well correlated with those of AQP2. Immunoprecipitation with a phospho-PKA substrates antibody followed by mass spectrometry analysis revealed that the leading candidate in this assay proved to be a lipopolysaccharide-responsive and beige-like anchor protein (LRBA). Phosphorylation levels of LRBA was nearly perfectly correlated with those of AQP2.
2022-07-23 | PXD033852 | Pride
Project description:Signal transduction plays a crucial role in defending against external environmental challenges, which can modulate the cellular response to external stimuli. cAMP/PKA signaling pathway is one of the most important signaling circuits and is evolutionarily conserved in eukaryotes. A. oligospora is a typical nematode-trapping fungi that can specialize adhesive network traps to kill nematodes after sensing the signals. To elucidate the biological roles of cAMP-PKA signaling pathway, we characterized an adenylate cyclase orthologous protein, AoAcy, a cAMP-dependent protein kinase regulator, AoPKaR, and two cAMP-dependent protein kinase catalytic subunits, AoPKaCs in A. oligospora. Furthermore, phenotypic analysis of the gene disruption strains showed that the deletion of AoAcy resulted in a significant decrease in the content of cAMP and arthrobotrisins, and the results indicated that AoAcy, AoPKaR and AoPKaC1 were involved in the hyphae growth, trap morphogenesis, sporulation, stress resistance and autophagy. In addition, AoAcy and AoPKaC1 were also participated in the regulation of mitochondria, thereby affecting energy metabolism. While AoPKaC2 only affected sporulation, the number of nuclei and autophagy. Collectively, these findings highlight the essential role of cAMP/PKA signaling pathway in A. oligospora and provide insights into the regulation mechanisms of signaling pathways in trap formation and sporulation.
2022-08-13 | GSE210886 | GEO
Project description:Abstract Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (CPT-cAMP), a PKA-selective cAMP analog, alters the expression of ~4500 of ~13,600 unique genes. By contrast, gene expression was unaltered in Kin– S49 cells (that lack PKA) incubated with CPT-cAMP. Changes in mRNA and protein expression of several cell-cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2 h, CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements (CRE) within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of CRE-containing genes and secondary networks that include the circadian clock. Keywords: time-course
2005-04-15 | GSE2413 | GEO
Project description:The conserved cAMP-dependent protein kinase (PKA) holoenzyme is composed of two catalytic and two regulatory subunits. It plays critical roles in the regulation of many biological processes in eukaryotic organisms. In the human fungal pathogen Candida albicans, the PKA kinase has been extensively investigated for its importance in the regulation of morphological transitions and virulence. It has been long thought that the PKA catalytic subunit is essential for cell viability in C. albicans. Paradoxically, the single adenylyl cyclase-encoding gene, CRY1, which is required for the production of cAMP in C. albicans, is not essential for cell growth. In this study, we successfully generated a null double mutant of TPK1 and TPK2 (tpk2/tpk2 tpk1/tpk1 or t2t1), which encode two isoforms of the PKA catalytic subunit in C. albicans. We reevaluated the roles of the PKA catalytic subunit in cell growth and phenotypic transitions. Inactivation of the PKA catalytic subunit by deletion of both TPK1 and TPK2 blocked filamentation and dramatically attenuated the ability of white-to-opaque switching, but promoted sexual mating in C. albicans. Tpk2 plays a major role in these regulations, while Tpk1 generally functions as a negative regulator in morphological transitions and sexual mating. A comparative transcriptomic analysis demonstrated that the t2t1 and cyr1/cyr1 mutants exhibited similar global gene expression profiles. Compared to the WT strain, the general transcriptional activity and expression of genes involved in metabolism, translation, biosynthesis, adhesion and filamentation are significantly decreased in both the t2t1 and cyr1/cyr1 mutants. And a portion of stress-response and cell wall-related genes were upregulated in these mutants, which is consistent with their increased ability of anti-stresses. To further explore the global regulatory role of the PKA kinase, we performed quantitative phosphoproteomics analysis. Combining with bioinformatics analyses, we identified 181 potential PKA phosphorylation targets, which represent 148 unique proteins involved in a wide spectrum of biological processes. Cell wall and membrane-related proteins (e.g. Ecm3, Bni1, and Smi1) were enriched in Tpk1-specific targets, while Tpk2-specific substrates include transporters, filamentation and cytoskeleton-related proteins (e.g. Smf3, Sep7, and Mhp1). There were also many Tpk1 and Tpk2 overlapped and coordinately regulated-substrates. Our study clarifies the essentiality of the PKA catalytic subunit and shed new insights into the global regulatory features of the cAMP/PKA pathway in C. ablicans. The t2t1 null mutant generated in this study would also be a new resource for the field to study this important pathway.
2017-08-18 | GSE92621 | GEO
Project description:The calcium-calmodulin (Ca2+-CaM) dependent protein kinase kinase-2 (CaMKK2) is activated by increases in intracellular Ca2+ and is a key regulator of cellular and wholebody energy metabolism. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma and metabolic derangements induced by a high-fat diet, therefore elucidating the intracellular mechanisms that inactivate CaMKK2 has important therapeutic implications. Here we show that stimulation of cyclic AMP (cAMP)-dependent protein kinase (PKA) signaling in cells inactivates CaMKK2 by phosphorylation of three conserved serine residues. PKA-dependent phosphorylation of Ser495 directly impairs Ca2+-CaM activation, whereas phosphorylation of Ser100 and Ser511 mediate recruitment of 14-3-3 adaptor proteins that hold CaMKK2 in the inactivated state by preventing dephosphorylation of phospho-Ser495. We also report the crystal structure of 14-3-3z bound to a synthetic diphosphorylated peptide that reveals how the canonical (Ser511) and non-canonical (Ser100) 14-3-3 consensus sites on CaMKK2 co-operate to bind 14-3-3 proteins. Our findings provide a detailed mechanistic insight into how cAMP-PKA signaling inactivates CaMKK2 and reveals a pathway to inhibit CaMKK2 with potential for treating human diseases.
2020-11-06 | PXD020133 | Pride