PTGES3

PTGES3, also known as the p23 co‑chaperone protein, encodes a small acidic protein that participates in the Hsp90 chaperone machinery. The gene is located on human chromosome 11 and is highly conserved among vertebrates and invertebrates. The resulting protein is approximately 152–170 amino acids long and is characterized by a leucine‑rich, acidic N‑terminal region that mediates interaction with Hsp90.

p23 binds to the ATP‑bound form of Hsp90, stabilizing the closed conformation of the chaperone complex and suppressing its ATPase activity. By doing so, PTGES3 promotes the proper folding and activation of a wide array of client proteins, including steroid hormone receptors, kinases, and transcription factors. The co‑chaperone also interacts with Hsp70, forming part of a larger protein maturation complex. PTGES3 has been implicated in the regulation of signal transduction pathways that govern cell proliferation and differentiation.

Although originally reported as a prostaglandin E synthase due to sequence homology, functional studies have shown that PTGES3 lacks enzymatic activity in prostaglandin production. Instead, its major role lies in protein folding. Elevated expression of PTGES3 has been observed in several malignancies, such as breast and prostate cancer, where it may contribute to tumor cell survival by enhancing the stability of oncogenic client proteins. Consequently, PTGES3 is being investigated as a potential biomarker and therapeutic target in cancer and other diseases associated with protein misfolding.

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