PDIA3

PDIA3, Protein disulfide-isomerase A3, alias 58 kDa glucose-regulated protein, 58 kDa microsomal protein (p58), Disulfide isomerase ER- 60. it is a member of the protein disulfide isomerase (PDI) family, an enzyme that catalyzes the formation of disulfide bonds in the endoplasmic reticulum and plays a crucial role in protein folding and quality control. pDIA3 acts as a molecular chaperone involved in the proper folding, assembly, and secretion of proteins, and it is especially highly expressed in cellular stress responses and is capable of intercepting apoptotic cell death associated with endoplasmic reticulum stress.

The biological significance of PDIA3 is broad, its expression is elevated in about 70% of cancers and is associated with low invasiveness, survival and metastatic capacity of tumor cells.PDIA3 is also significantly associated with immune activation markers, cancer immune cell infiltration and immunomodulators, and in particular significantly predicts response to anti-PDL1 therapy. In addition, PDIA3 has a regulatory role in the T-cell receptor (TCR) signaling pathway, which promotes T-cell activation, participates in the regulation of the T-cell TCR signaling pathway, and affects the phosphorylation level of the ZAP70 protein, the expression of CD69, and the secretion of IL-2, as well as the NF-κB signaling pathway. Therefore, PDIA3 not only plays a role in protein synthesis, degradation and secretion, shaping the tumor microenvironment, but also is a potent biomarker of cancer prognosis and immunotherapy response, with potential as an anticancer therapeutic target.