Understanding the complex genetic makeup underlying congenital anomalies of the kidney and urinary tract (CAKUT) is of primary importance to improve diagnosis, stratify risk for later-onset complications, and develop therapeutic strategies.Saisawat et al. used homozygosity mapping coupled with next-generation sequencing to identify recessive mutations in TRAP1 in families with isolated CAKUT and with VACTERL association.
As possible outputs for this antioxidant deficiency, we found an increase of intracellular reactive oxygen species generation in OA chondrocytes and also verified an OA-dependent increase in the mitochondrial tumor necrosis factor-alpha receptor-associated protein 1 (TRAP1), a chaperone with a reported reactive oxygen species antagonist role.
Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.
Consistently, a BRAF dominant-negative mutant prevents TRAP1 serine phosphorylation and restores drug sensitivity in BRAFV600E CRC drug-resistant cells with high TRAP1 levels.
This study is the first demonstration that TRAP1 regulates stemness and Wnt/β-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics.
The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry.
The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk.
This study demonstrates for the first time that TRAP1 is associated with ribosomes and with several translation factors in colon carcinoma cells and, remarkably, is found co-upregulated with some components of the translational apparatus (eIF4A, eIF4E, eEF1A and eEF1G) in human colorectal cancers, with potential new opportunities for therapeutic intervention in humans.
As an elevated expression of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 was associated with poorer OS outcomes in patients with NSCLC, these HSP90 members may be potential prognostic biomarkers and drug targets for the treatment of NSCLC.
Here we investigated the different susceptibility of glutamine-independent and glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib-triphenylphosphonium (G-TPP).