|Figure 2: Posttranslational modifications play a crucial role in the regulation of GR activity
which impacts on the neuroendocrine and immune regulatory pathways. GCs are the downstream
effectors of the HPA axis response. They play a key role in the communication between
the neuroendocrine and immune systems to ensure homeostasis. GCs impact on both HPA-mediated
stress responses and immune responses. GCs effects are mainly mediated through binding
to the GR. A series of mechanisms regulate GR activity to ensure GCs specificity.
These mechanisms include modulation of GR by posttranslational modifications (PTMs).
Different cellular stressors and also hormone binding can modulate PTMs of target
proteins. PTMs do not only target GR but also key molecules involved in the regulation
of GR activity such as the cochaperone/chaperone heterocomplex and GR coactivators
and corepressors. PTMs regulate protein properties including stability, structure,
function, activity, intracellular localization, and interaction with other proteins
during cellular processes determining the final outcome. This review focuses on PTMs
that target GR and GR modulators such as Hsp90, FKBP52, and GRIP1, fine-tuning GR
transcriptional outcome, thus adding complexity and specificity to GCs action. GR
and Hsp90 activity is modified by SUMOylation, ubiquitination, acetylation, and phosphorylation.
Hsp90 is further regulated by methylation by methylatransferases (MT). GRIP1 is targeted
by phosphorylation, ubiquitination, and sumoylation. Finally, FKBP52 by phosphorylation
and p300 by methylation.