GRP94

Heat shock protein (HSP) molecular chaperones are environmental stress-inducible gene products. The human HSP 90 family includes 17 genes that fall into four classes: HSP90AA, HSP90AB, HSP90B and TRAP. HSP 90 family members guide the normal folding, intracellular disposition and proteolytic turnover of many key regulators of cell growth, differentiation and survival. HSP 90α, also designated HSP90A, HSP 86 and LPS-associated protein 2 (LAP2), is a cytosolic enhancer of inducible nitric-oxide synthase (iNOS), with chaperone activity that is important for the transcriptional activity of p53. HSP 90β, also designated HSP90B, HSP 84 and HSPC2, is a cytosolic protein that participates in signaling pathways with PKC e to protect cells from external damage, particularly in heat shock-mediated events. GRP 94, also known as tumor rejection antigen 1 (TRA1), ECGP and GP96, localizes to the ER, is highly expressed in BGC-823 human gastric carcinoma cells and is upregulated in human endothelial cells in response to hypoxia by HIF-1. TRAP1 (TNF receptor-associated protein 1), also designated HSP 75) is a mitochondrial matrix component that plays a role in the induction of apoptosis in response to reactive oxygen species.