Am J Cancer Res 2012;2(2):235-248
Review Article
New insights into TRAP1 pathway
Danilo Swann Matassa, Maria Rosaria Amoroso, Francesca Maddalena, Matteo Landriscina, Franca Esposito
1Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, Naples 80131, Italy;
2Laboratorio di Oncologia Molecolare, IRCCS-CROB Rionero in Vulture (PZ), Italy; 3Clinical Oncology Unit, Department of
Medical Sciences,University of Foggia, Foggia, Italy
Received February 6, 2012; accepted February 15, 2012; Epub February 19, 2012; Published February 28, 2012
Abstract: Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a mitochondrial heat shock protein involved in the
protection from DNA damages and apoptosis induced by oxidants and several other stress conditions. Despite the well-
characterized role in the regulation of mitochondrial integrity, through the interaction with cyclophilin D, a mitochondrial
permeability transition pore regulator, several recent studies contributed to draw a more complex “picture” of the TRAP1 pathway:
most of these updated functions arise from the identification of novel specific TRAP1 “client” proteins and from the recent
discovery of multiple subcellular localizations/functions for this chaperone. This review briefly highlights some general features
of TRAP1, and among others its role in cytoprotection, summarizing many different functions, which contribute to its protective
role upon several stress inducers. Of note, particular emphasis is given to the recent findings on the regulation of Endoplasmic
Reticulum stress and protein quality control by TRAP1, as well as to its role in regulating calcium homeostasis throughout its
client protein sorcin. Starting from the above observations a preliminary “TRAP1 signature” is provided and a new intriguing and
interesting field to explore is discussed. Several questions are still open given the complexity of such mechanisms. However, by
translating these recent insights at the molecular and cellular levels into personalized individual anticancer treatments,
designing novel strategies based on the simultaneous inhibition of multiple tumor-specific pathways, and contemplating
subcellular-targeted approaches aimed at reverting drug resistance and improving antitumor activity the struggle to combat
cancer become more successful and closer. (AJCR00000108).
Keywords: TRAP1, HSP90, apoptosis, mitochondria, endoplasmic reticulum, stress, cancer, drug resistance
Address all correspondence to:
Dr. Franca Esposito
Dipartimento di Biochimica e Biotecnologie Mediche
Università degli Studi di Napoli Federico II
Via S. Pansini 5 – 80131 Napoli, Italy.
Tel: ++39 081 7463145; Fax: ++39 081 7464359
E-mail: franca.esposito@unina.it.
Dr. Matteo Landriscina
Dipartimento di Scienze Mediche e del Lavoro
Università degli Studi di Foggia
Viale Pinto, 1 – 71100 Foggia, Italy.
Tel: ++39 0881 736241; Fax: ++39 0881 733614
E-mail: m.landriscina@unifg.it
Review Article
New insights into TRAP1 pathway
Danilo Swann Matassa, Maria Rosaria Amoroso, Francesca Maddalena, Matteo Landriscina, Franca Esposito
1Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, Naples 80131, Italy;
2Laboratorio di Oncologia Molecolare, IRCCS-CROB Rionero in Vulture (PZ), Italy; 3Clinical Oncology Unit, Department of
Medical Sciences,University of Foggia, Foggia, Italy
Received February 6, 2012; accepted February 15, 2012; Epub February 19, 2012; Published February 28, 2012
Abstract: Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a mitochondrial heat shock protein involved in the
protection from DNA damages and apoptosis induced by oxidants and several other stress conditions. Despite the well-
characterized role in the regulation of mitochondrial integrity, through the interaction with cyclophilin D, a mitochondrial
permeability transition pore regulator, several recent studies contributed to draw a more complex “picture” of the TRAP1 pathway:
most of these updated functions arise from the identification of novel specific TRAP1 “client” proteins and from the recent
discovery of multiple subcellular localizations/functions for this chaperone. This review briefly highlights some general features
of TRAP1, and among others its role in cytoprotection, summarizing many different functions, which contribute to its protective
role upon several stress inducers. Of note, particular emphasis is given to the recent findings on the regulation of Endoplasmic
Reticulum stress and protein quality control by TRAP1, as well as to its role in regulating calcium homeostasis throughout its
client protein sorcin. Starting from the above observations a preliminary “TRAP1 signature” is provided and a new intriguing and
interesting field to explore is discussed. Several questions are still open given the complexity of such mechanisms. However, by
translating these recent insights at the molecular and cellular levels into personalized individual anticancer treatments,
designing novel strategies based on the simultaneous inhibition of multiple tumor-specific pathways, and contemplating
subcellular-targeted approaches aimed at reverting drug resistance and improving antitumor activity the struggle to combat
cancer become more successful and closer. (AJCR00000108).
Keywords: TRAP1, HSP90, apoptosis, mitochondria, endoplasmic reticulum, stress, cancer, drug resistance
Address all correspondence to:
Dr. Franca Esposito
Dipartimento di Biochimica e Biotecnologie Mediche
Università degli Studi di Napoli Federico II
Via S. Pansini 5 – 80131 Napoli, Italy.
Tel: ++39 081 7463145; Fax: ++39 081 7464359
E-mail: franca.esposito@unina.it.
Dr. Matteo Landriscina
Dipartimento di Scienze Mediche e del Lavoro
Università degli Studi di Foggia
Viale Pinto, 1 – 71100 Foggia, Italy.
Tel: ++39 0881 736241; Fax: ++39 0881 733614
E-mail: m.landriscina@unifg.it
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American Journal of Cancer Research
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