Prostaglandin E synthase 3 (p23) (PTGES3)

Prostaglandin E synthase 3 (PTGES3), widely known as p23, is a critical cytosolic co-chaperone that regulates the activity of the heat shock protein 90 (HSP90) machinery [UniProt Q15185]. It specifically binds to the ATP-bound state of HSP90, stabilizing the chaperone in a closed conformation that is essential for the final stages of folding and activation of 'client' proteins, including steroid hormone receptors (such as the glucocorticoid and estrogen receptors) and various oncogenic kinases [PubMed: 10409743]. In addition to its chaperone function, p23 acts as a terminal enzyme in the arachidonic acid pathway, converting prostaglandin H2 into prostaglandin E2 (PGE2), a key lipid mediator of inflammation and pain [PubMed: 11034310]. In many human cancers, p23 is overexpressed and correlates with increased tumor aggressiveness and poor prognosis, as it maintains the stability of proteins required for cell survival and proliferation [PubMed: 23536446]. Therapeutic targeting of p23 aims to disrupt its interaction with HSP90 or inhibit its enzymatic activity, offering a dual mechanism to promote the degradation of oncogenic drivers and reduce pro-inflammatory signaling [PubMed: 19435913].

Other names

p23Cytosolic prostaglandin E2 synthasecPGESTelomerase-binding proteinTEBPHSP90 co-chaperone p23

Inhibition of the p23 co-chaperone activity disrupts the HSP90 folding cycle, leading to the ubiquitin-proteasome-mediated degradation of client proteins such as steroid receptors and oncogenic kinases, while simultaneously reducing the synthesis of the pro-inflammatory mediator prostaglandin E2 [PubMed: 19435913, PubMed: 11034310].