Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate synthesis is the link between carbon and nitrogen metabolism. In Bacillus subtilis, glutamate is exclusively synthesized by the glutamate synthase encoded by the gltAB operon. The glutamate dehydrogenase RocG from B. subtilis is exclusively devoted to glutamate degradation rather than to its synthesis. The expression of the gltAB operon is induced by glucose and ammonium and strongly repressed by arginine. Regulation by glucose and arginine depends on the transcriptional activator protein GltC. The gltAB operon is constitutively expressed in a rocG mutant strain, but the molecular mechanism of negative control of gltAB expression by RocG has so far remained unknown. We studied the role of RocG in the intracellular accumulation of GltC. Furthermore, we considered the possibility that RocG might act as a transcription factor and be able to inhibit the expression of gltAB either by binding to the mRNA or to the promoter region of the gltAB operon. Finally, we asked whether a direct binding of RocG to GltC could be responsible for the inhibition of GltC. The genetic and biochemical data presented here show that the glutamate dehydrogenase RocG is able to bind to and concomitantly inactivate the activator protein GltC. This regulatory mechanism by the bifunctional enzyme RocG allows the tight control of glutamate metabolism by the availability of carbon and nitrogen sources.
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PMID:A regulatory protein-protein interaction governs glutamate biosynthesis in Bacillus subtilis: the glutamate dehydrogenase RocG moonlights in controlling the transcription factor GltC. 1760 97

Glutamate, the major excitatory amino acid, activates a wide variety of signal transduction cascades. This neurotransmitter is involved in photic entrainment of circadian rhythms, which regulate physiological and behavioral functions. The circadian clock in vertebrates is based on a transcription-translation feedback loop in which Brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) acts as transcriptional activator of others clock genes. This protein is expressed in nearly all suprachiasmatic nucleus neurons, as well as in the granular layer of the cerebellum. In this context, we decided to investigate the role of glutamate in the molecular mechanisms involved in the processes of transcription/translation of BMAL1 protein. To this end, primary cultures of chick cerebellar Bergmann glial cells were stimulated with glutamatergic ligands and we found that BMAL1 levels increased in a dose- and time dependent manner. Additionally, we studied the phosphorylation of serine residues in BMAL1 under glutamate stimulation and we were able to detect an increase in the phosphorylation of this protein. The increased expression of BMAL1 is most probably the result of a stabilization of the protein after it has been phosphorylated by the cyclic AMP-dependent protein kinase and/or the Ca(2+)/diacylglycerol dependent protein kinase. The present results strongly suggest that glutamate participates in regulating BMAL1 in glial cells and that these cells might prove to be important in the control of circadian rhythms in the cerebellum.
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PMID:Glutamate-Dependent BMAL1 Regulation in Cultured Bergmann Glia Cells. 2574 91