Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeine, theophylline, and theobromine are the most well-known members of methylxanthines. Caffeine-induced serine/arginine-rich splicing factor 2, SRSF2, and SRSF3 are required for the alternative splicing of a subset of cancer-associated genes. However, it remains to be investigated whether and how theophylline and theobromine as well as caffeine exert their antitumor effects through mediating the alternative splicing process. Here, we reveal that theophylline down-regulated SRSF3 expression and switched p53 from alpha into a beta isoform as caffeine did in HeLa and MCF-7 cells via the reverse-transcriptase polymerase chain reaction and Western blot analysis. Further functional studies show that theophylline induced cellular apoptosis, senescence, and decreased colony formation. Interestingly, theophylline had a suppressive effect on cellular proliferation, whereas caffeine enhanced cellular proliferation rates via the 5-bromo-2-deoxyuridine analysis. Theophylline and caffeine had no effect on MCF-10A cells, which is a normal breast cell line. Our results provide an insight that theophylline as well as caffeine could be repurposed as antitumor leading compounds via the downregulation of splicing factor SRSF3 and its target genes.
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PMID:Theophylline exhibits anti-cancer activity via suppressing SRSF3 in cervical and breast cancer cell lines. 2925 78

The type 2A protein phosphatases (PP2As) are holoenzymes in all eukaryotes but their activators remain unknown in filamentous fungi. Fusarium graminearum contains three PP2As (FgPp2A, FgSit4, and FgPpg1), which play critical roles in fungal growth, development, and virulence. Here, we identified two PP2A activators (PTPAs), FgRrd1 and FgRrd2, and found that they control PP2A activity in a PP2A-specific manner. FgRrd1 interacts with FgPpg1, but FgRrd2 interacts with FgPp2A and very weakly with FgSit4. Furthermore, FgRrd2 activates FgPp2A via regulating FgPp2A methylation. Phenotypic assays showed that FgRrd1 and FgRrd2 regulate mycelial growth, conidiation, sexual development, and lipid droplet biogenesis. More importantly, both FgRrd1 and FgRrd2 interact with RNA polymerase II, subsequently modulating its enrichments at the promoters of mycotoxin biosynthesis genes, which is independent on PP2A. In addition, FgRrd2 modulates response to phenylpyrrole fungicide, via regulating the phosphorylation of kinase FgHog1 in the high-osmolarity glycerol pathway, and to caffeine, via modulating FgPp2A methylation. Taken together, results of this study indicate that FgRrd1 and FgRrd2 regulate multiple physiological processes via different regulatory mechanisms in F. graminearum, which provides a novel insight into understanding the biological functions of PTPAs in fungi.
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PMID:The Activators of Type 2A Phosphatases (PP2A) Regulate Multiple Cellular Processes Via PP2A-Dependent and -Independent Mechanisms in Fusarium graminearum. 2987 64


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