Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Selected targets of GCR-alpha


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Selected targets of GCR-alpha

Selected targets of GCR-alpha

Glucocorticoid receptors are nuclear hormone receptors that belong to the superfamilyof ligand-activated transcription factors. Nuclear receptor subfamily 3 group C member 1( GCR-alpha ) is the major isoform of glucocorticoid receptors expressed in manytissues. Like other members of the family, the GCR-alpha possesses a modularstructure consisting of three major domains: N-terminal (NTD), DNA binding (DBD), andligand binding (LBD). Glucocorticoid molecules bind equimolarly toGCR-alpha and cause dimerization and translocation of the protein to the nucleus,where it bind to glucocorticoid response elements (GRE) on glucocorticoid-responsivegenes, resulting in increased transcription of target genes [1].

Glucocorticoids are widely used for the suppression of inflammation in chronicinflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel diseaseand autoimmune diseases [2], [3]. This effect may be realizedvia GCR-alpha -dependent transcriptional regulation of immunological andinflammatory signaling proteins, such as Interleukin 4 ( IL-4 ) [4],Interleukin 8 ( IL-8 ) [5], Interleukin 6 ( IL-6 ) [6], Toll-like receptor 2 ( TLR2 ) [7] and others.

Natural Glucocorticoids are essential components of the body neuroendocrinesystem, modulating the physiological homeostasis and coordinating the adaptive responsesto stressors. Whereas physiological levels of Glucocorticoids are required forproper metabolic control, excessive Glucocorticoids action has been tied to avariety of pandemic metabolic diseases, such as type II diabetes and obesity [8], [9], [10]. GCR-alpha regulates transcriptionof Insulin [11], Insulin receptor [12], Insulin-likegrowth factor binding protein 1 ( IBP1 ) [13], Leptin [14], LIPIN1 [15].

GCR-alpha is essential for regulation of developmental signaling. It playsimportant role in synaptic maturation [16], gametogenesis [17]and pathological processes such as osteoporosis [18], [19],muscular dystrophy [20] and others. These effects may be realized viaGCR-alpha -dependent regulation transcription of developmental and cytoskeletalsignaling proteins, such as Follicle stimulating hormone beta polypeptide (FSH-beta ) [17], Tumor necrosis factor (ligand) superfamily member 11( RANKL(TNFSF11) ) [21], and Elastin [22].

In addition, GCR-alpha plays important role in toxicological processesstimulating transcription of xenobiotic-sensing receptors Nuclear receptor subfamily 1group I members 2 and 3 ( PXR and CAR ) [23] and someCytochromes P450 [24], [25].