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

Matassa, D., Agliarulo, I., Amoroso, M., Maddalena, F., Sepe, L., Ferrari, M., et al. (2014). TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors. MOLECULAR ONCOLOGY, 8(8), 1482-1494 [10.1016/j.molonc.2014.06.003].

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

LORENI, FABRIZIO;
2014-12-01

Abstract

TNF receptor-associated protein 1 (TRAP1) is an HSP90 chaperone involved in stress protection and apoptosis in mitochondrial and extramitochondrial compartments. Remarkably, aberrant deregulation of TRAP1 function has been observed in several cancer types with potential new opportunities for therapeutic intervention in humans. Although previous studies by our group identified novel roles of TRAP1 in quality control of mitochondria-destined proteins through the attenuation of protein synthesis, molecular mechanisms are still largely unknown. To shed further light on the signaling pathways regulated by TRAP1 in the attenuation of protein synthesis, this study demonstrates that the entire pathway of cap-mediated translation is activated in cells following TRAP1 interference: consistently, expression and consequent phosphorylation of p70S6K and RSK1, two translation activating kinases, are increased upon TRAP1 silencing. Furthermore, we show that these regulatory functions affect the response to translational stress and cell migration in wound healing assays, processes involving both kinases. Notably, the regulatory mechanisms controlled by TRAP1 are conserved in colorectal cancer tissues, since an inverse correlation between TRAP1 and p70S6K expression is found in tumor tissues, thereby supporting the relevant role of TRAP1 translational regulation in vivo. Taken as a whole, these new findings candidate TRAP1 network for new anti-cancer strategies aimed at targeting the translational/quality control machinery of tumor cells.
dic-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
TRAP1; Ribavirin; Wound healing; Colorectal carcinoma; Translation control; Cell migration
Matassa, D., Agliarulo, I., Amoroso, M., Maddalena, F., Sepe, L., Ferrari, M., et al. (2014). TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors. MOLECULAR ONCOLOGY, 8(8), 1482-1494 [10.1016/j.molonc.2014.06.003].
Matassa, D; Agliarulo, I; Amoroso, M; Maddalena, F; Sepe, L; Ferrari, M; Sagar, V; D'Amico, S; Loreni, F; Paolella, G; Landriscina, M; Esposito, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/119263
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