Protein_Domain

Part:BBa_K3704000

Designed by: Kong Yangyang   Group: iGEM20_ECNUAS   (2020-10-17)
Revision as of 15:21, 26 October 2020 by Zhuke18 (Talk | contribs) (Biology)


GR

BBa_K3704000 is a protein domain of the glucocorticoid receptor (PubMed:27120390). Has a dual mode of action: a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation, and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner that recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity).

Biology and Contribution

Composite part BBa_K3704000 is the coding sequence of the glucocorticoid receptor (GR). GR belongs to the steroid hormone receptor subclass of nuclear receptors, which controls physiological processes by activating and inhibiting specific target genes (PMID: 15379669). The ligand-activated receptor dimer activates gene expression by binding to GRE in the promoter region of the glucocorticoid regulatory gene.

Engineering Success

Verify the function GR using a luciferase reporting system In order to test the function of the GR, a recombinant GR producing construct (BBa_K3704002) and a luciferase reporting system (two constructs contain parts BBa_K3704001 and BBa_K3522012, respectively) were co-transfected into HEK293T cells. With the addition of GR agonist (Dexamethasone, Dex) into the cell culture, a significant value of luciferase activity was detected (Figure 1). While, in the presence of Dex and a GR antagonist (Mifepristone, Mife), the luciferase activity reduced to a value similar to the blank control (DMSO).

Figure 1. Relative luciferase activity in the presence of GR agonist (Dexamethasone, Dex) and GR antagonist (Mifepristone, Mife).
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