GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life

Frontiers in Immunology
Ann Louw

Abstract

Pharmacologically, glucocorticoids, which mediate their effects via the glucocorticoid receptor (GR), are a most effective therapy for inflammatory diseases despite the fact that chronic use causes side-effects and acquired GC resistance. The design of drugs with fewer side-effects and less potential for the development of resistance is therefore considered crucial for improved therapy. Dimerization of the GR is an integral step in glucocorticoid signaling and has been identified as a possible molecular site to target for drug development of anti-inflammatory drugs with an improved therapeutic index. Most of the current understanding regarding the role of GR dimerization in GC signaling derives for dimerization deficient mutants, although the role of ligands biased toward monomerization has also been described. Even though designing for loss of dimerization has mostly been applied for reduction of side-effect profile, designing for loss of dimerization may also be a fruitful strategy for the development of GC drugs with less potential to develop GC resistance. GC-induced resistance affects up to 30% of users and is due to a reduction in the GR functional pool. Several molecular mechanisms of GC-mediated reductions in GR pool ha...Continue Reading

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Dec 14, 2019·Immunological Investigations·Madoka Koyanagi, Yutaka Arimura
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Sep 11, 2021·Journal of Chemical Information and Modeling·Haiyi ChenTingjun Hou
Oct 29, 2021·Biochemical Society Transactions·Filipp FrankXu Liu

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Methods Mentioned

BETA
NMR
co-immunoprecipitation
fluorescence correlation spectroscopy
ChIP-exo
ubiquitination
nuclear translocation

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