TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors

摘要: TNF receptor-associated protein 1 (TRAP1) is an HSP90 chaperone involved in stress protection and apoptosis mitochondrial extramitochondrial compartments. Remarkably, aberrant deregulation of TRAP1 function has been observed several cancer types with potential new opportunities for therapeutic intervention humans. Although previous studies by our group identified novel roles quality control mitochondria-destined proteins through the attenuation synthesis, molecular mechanisms are still largely unknown. To shed further light on signaling pathways regulated this study demonstrates that entire pathway cap-mediated translation activated cells following interference: consistently, expression consequent phosphorylation p70S6K RSK1, two activating kinases, increased upon silencing. Furthermore, we show these regulatory functions affect response to translational cell migration wound healing assays, processes involving both kinases. Notably, controlled conserved colorectal tissues, since inverse correlation between found tumor thereby supporting relevant role regulation in vivo. Taken as a whole, findings candidate network anti-cancer strategies aimed at targeting translational/quality machinery cells.