The Hsp9 molecular chaperones are ATP-dependent enzymes that maintain protein homeostasis and regulate many essential cellular processes. The mitochondrial Hsp9, TNF receptor-associated protein 1 (TRAP1), supports the folding and activity of electron transport components and is increasingly appreciated as a critical player in mitochondrial signaling. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 9 (HSP9) family that directly interacts with respiratory complexes, contributing to their stability and activity. TRAP1 could be a promising therapeutic target for glutamine-addicted cancer.
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