A very straight-forward and classic approach to characterize a new level of GR protein degradation.
Lysine 419 targets human glucocorticoid receptor for proteasomal degradation
Showing posts with label GR. Show all posts
Showing posts with label GR. Show all posts
Thursday, August 19, 2010
Thursday, July 8, 2010
GR and MeCP2
So, Freddy sent me a thesis written in 2006 from a German University. It is about a methyl CpG binding protein, called MeCP2, that suppresses GR-target genes. MeCP2 has been shown to be required for the normal function of neurons and is usually thought to act as a repressor of genes, including CRH (my favorite gene). Mutations in the MECP2 gene has been strongly linked to a neurodevelopmental disorder known as Rett Syndrome.
In this paper, they used a microarray analysis to compare gene expression from WT and MeCP2-null mice. They discovered that at least 5 of the 11 differentially regulated genes are GR target genes. They show by ChIP (your favorite technique!) that MeCP2 binds to the promoter region of FKBP5 and SGK1, suggesting a relationship between MeCP2 occupancy and gene expression. Its not very clear to me in the paper, but what is really novel in the thesis is that Dex prevents Mecp2 from binding to a GRE within the FKBP5 gene. This is prevented by RU486. Its in the last figure of the RESULTS Section found HERE.
The bigger picture here, I think, is how epigenetics, in particular, DNA methylation, is regulating the expression of these GR target genes in neurons. This has many implications for stress response since one of the identified genes, POMC, is a key player of the HPA axis and CRH also has been shown to be regulated by MeCP2.
In this paper, they used a microarray analysis to compare gene expression from WT and MeCP2-null mice. They discovered that at least 5 of the 11 differentially regulated genes are GR target genes. They show by ChIP (your favorite technique!) that MeCP2 binds to the promoter region of FKBP5 and SGK1, suggesting a relationship between MeCP2 occupancy and gene expression. Its not very clear to me in the paper, but what is really novel in the thesis is that Dex prevents Mecp2 from binding to a GRE within the FKBP5 gene. This is prevented by RU486. Its in the last figure of the RESULTS Section found HERE.
The bigger picture here, I think, is how epigenetics, in particular, DNA methylation, is regulating the expression of these GR target genes in neurons. This has many implications for stress response since one of the identified genes, POMC, is a key player of the HPA axis and CRH also has been shown to be regulated by MeCP2.
Tuesday, June 1, 2010
CDK5 Modulates the Transcriptional Activity of the Mineralocorticoid Receptor and Regulates Expression of BDNF
http://mend.endojournals.org/cgi/content/full/24/5/941#T1
Michael and this same group previously published a paper looking at the effect of cdk5 signaling on GR phosphorylation in neurons. Now they extend their study to MR and the effect of cdk5 on its transcriptional activity. In the process of identifying the phospho-sites induced by cdk5 on MR, they also show that cdk5 induces hGR phosphorylation by mass spec at S267 (one of the same BDNF induced phospho-sites that we identified in our lab).
This paper is not particularly innovative but they do "good" science to address the molecular affects of cdk5 on MR and GR with relevance to action in the nervous system.
Michael and this same group previously published a paper looking at the effect of cdk5 signaling on GR phosphorylation in neurons. Now they extend their study to MR and the effect of cdk5 on its transcriptional activity. In the process of identifying the phospho-sites induced by cdk5 on MR, they also show that cdk5 induces hGR phosphorylation by mass spec at S267 (one of the same BDNF induced phospho-sites that we identified in our lab).
This paper is not particularly innovative but they do "good" science to address the molecular affects of cdk5 on MR and GR with relevance to action in the nervous system.
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