TY - JOUR
T1 - TRAP1 revisited
T2 - Novel localizations and functions of a 'next-generation' biomarker (Review)
AU - Amoroso, Maria Rosaria
AU - Matassa, Danilo Swann
AU - Sisinni, Lorenza
AU - Lettini, Giacomo
AU - Landriscina, Matteo
AU - Esposito, Franca
PY - 2014
Y1 - 2014
N2 - In the last decade, the identification and characterization of novel molecular mechanisms and pathways involving the heat shock protein TRAP1/HSP75 in cancers and other diseases enhanced the scientific interest. Recent reports have shown that TRAP1 stays at the crossroad of multiple crucial processes in the onset of neoplastic transformation. In fact, TRAP1: i) contributes to the tumor's switch to aerobic glycolysis through the inhibition of succinate dehydrogenase, the complex II of the mitochondrial respiratory chain; ii) is part of a pro-survival signaling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and protects mitochondria against damaging stimuli via a decrease of ROS generation; iii) controls protein homeostasis through a direct involvement in the regulation of protein synthesis and protein co-translational degradation. Therefore, TRAP1 seems to be a central regulatory protein with balancing functions at the intersection of different metabolic processes during the neoplastic transformation. For this reason, it can be considered at the same time an attractive target for the development of novel anticancer strategies and a promising study model to understand the biology of tumor cells at a systemic level. This review summarizes the most recent advances in TRAP1 biology and proposes a new comprehensive view of its functions.
AB - In the last decade, the identification and characterization of novel molecular mechanisms and pathways involving the heat shock protein TRAP1/HSP75 in cancers and other diseases enhanced the scientific interest. Recent reports have shown that TRAP1 stays at the crossroad of multiple crucial processes in the onset of neoplastic transformation. In fact, TRAP1: i) contributes to the tumor's switch to aerobic glycolysis through the inhibition of succinate dehydrogenase, the complex II of the mitochondrial respiratory chain; ii) is part of a pro-survival signaling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and protects mitochondria against damaging stimuli via a decrease of ROS generation; iii) controls protein homeostasis through a direct involvement in the regulation of protein synthesis and protein co-translational degradation. Therefore, TRAP1 seems to be a central regulatory protein with balancing functions at the intersection of different metabolic processes during the neoplastic transformation. For this reason, it can be considered at the same time an attractive target for the development of novel anticancer strategies and a promising study model to understand the biology of tumor cells at a systemic level. This review summarizes the most recent advances in TRAP1 biology and proposes a new comprehensive view of its functions.
KW - Anticancer agents
KW - Apoptosis
KW - Heat shock proteins
KW - Protein quality control
KW - TRAP1
KW - Tumor biomarker
UR - http://www.scopus.com/inward/record.url?scp=84904396628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904396628&partnerID=8YFLogxK
U2 - 10.3892/ijo.2014.2530
DO - 10.3892/ijo.2014.2530
M3 - Article
C2 - 24990602
AN - SCOPUS:84904396628
VL - 45
SP - 969
EP - 977
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -