Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Danilo Swann MatassaEmail author
  • Ilenia Agliarulo
  • Maria Rosaria Amoroso
  • Rosario Avolio
  • Matteo LandriscinaEmail author
  • Franca EspositoEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101888


Historical Background

TNF receptor-associated protein 1 (TRAP1) was firstly identified by a yeast-based two-hybrid system as a novel protein binding the intracellular domain of the type 1 receptor for tumor necrosis factor (TNFR-1IC), hence its name. The protein immediately showed strong sequence homology with members of the heat shock proteins 90-kDa (HSP90) family and variable expression levels in human skeletal muscle, liver, heart, brain, kidney, pancreas, lung, and placenta and in eight different transformed cell lines (Song et al. 1995). A second, independent yeast two-hybrid screening led to the identification of a new heat shock protein functioning as a molecular chaperone for the retinoblastoma protein (Rb). Antibodies prepared against fusion protein between glutathione S-transferase and domains of this new heat shock protein...

This is a preview of subscription content, log in to check access.


  1. Agliarulo I, Matassa DS, Amoroso MR, Maddalena F, Sisinni L, Sepe L, Ferrari MC, Arzeni D, Avolio R, Paolella G, Landriscina M, Esposito F. TRAP1 controls cell migration of cancer cells in metabolic stress conditions: correlations with AKT/p70S6K pathways. Biochim Biophys Acta. 2015;1853:2570–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Amoroso MR, Matassa DS, Sisinni L, Lettini G, Landriscina M, Esposito F. TRAP1 revisited: novel localizations and functions of a “next-generation” biomarker. Int J Oncol. 2014;45(3):969–77.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Amoroso MR, Matassa DS, Agliarulo I, Avolio R, Lu H, Sisinni L, Lettini G, Gabra H, Landriscina M, Esposito F. TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial–mesenchymal transition. Cell Death Dis. 2016; 7:e2522.  https://doi.org/10.1038/cddis.2016.400.CrossRefGoogle Scholar
  4. Cechetto JD, Gupta RS. Immunoelectron microscopy provides evidence that tumor necrosis factor receptor-associated protein 1 (TRAP-1) is a mitochondrial protein which also localizes at specific extramitochondrial sites. Exp Cell Res. 2000;260(1):30–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Chen CF, Chen Y, Dai K, Chen PL, Riley DJ, Lee WH. A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. Mol Cell Biol. 1996;16(9):4691–9.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Condelli V, Piscazzi A, Sisinni L, Matassa DS, Maddalena F, Lettini G, Simeon V, Palladino G, Amoroso MR, Trino S, Esposito F, Landriscina M. TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell cycle progression: a novel target for BRAF-mutated colorectal tumors. Cancer Res. 2014;74(22):6693–704.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Condelli V, Maddalena F, Sisinni L, Lettini G, Matassa DS, Piscazzi A, Palladino G, Amoroso MR, Esposito F, Landriscina M. Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: a novel strategy for human BRAF-driven colorectal carcinoma. Oncotarget. 2015;6(26):22298–309.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Felts SJ, Owen BA, Nguyen P, Trepel J, Donner DB, Toft DO. The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. J Biol Chem. 2000;275(5):3305–12.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Fismen S, Thiyagarajan D, Seredkina N, Nielsen H, Jacobsen S, Elung-Jensen T, Kamper AL, Johansen SD, Mortensen ES, Rekvig OP. Impact of the tumor necrosis factor receptor-associated protein 1 (Trap 1) on renal DNaseI shutdown and on progression of murine and human lupus nephritis. Am J Pathol. 2013;182(3):688–700.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ, Altieri DC. Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell. 2007 Oct 19;131(2):257–70.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Lavery LA, Partridge JR, Ramelot TA, Elnatan D, Kennedy MA, Agard DA. Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism. Mol Cell. 2014;53(2):330–43.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, Languino LR, Altieri DC. Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer. Am J Pathol. 2010;176(1):393–401.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Lettini G, Sisinni L, Condelli V, Matassa DS, Simeon V, Maddalena F, Gemei M, Lopes E, Vita G, Del Vecchio L, Esposito F, Landriscina M. TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma. Cell Death Differ. 2016;23(11):1792–803.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Lisanti S, Tavecchio M, Chae YC, Liu Q, Brice AK, Thakur ML, Languino LR, Altieri DC. Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks. Cell Rep. 2014;8(3):671–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lisanti S, Garlick DS, Bryant KG, Tavecchio M, Mills GB, Lu Y, Kossenkov AV, Showe LC, Languino LR, Altieri DC. Transgenic expression of mitochondrial chaperone TRAP1 accelerates prostate cancer development. J Biol Chem. 2016;291:25247–54.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Matassa DS, Agliarulo I, Amoroso MR, Maddalena F, Sepe L, Ferrari MC, Sagar V, D’Amico S, Loreni F, Paolella G, Landriscina M, Esposito F. TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: Relevance in human colorectal tumors. Mol Oncol. 2014;8(8):1482–94.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Matassa DS, Amoroso MR, Lu H, Avolio R, Arzeni D, Procaccini C, Faicchia D, Maddalena F, Simeon V, Agliarulo I, Zanini E, Mazzoccoli C, Recchi C, Stronach E, Marone G, Gabra H, Matarese G, Landriscina M, Esposito F. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer. Cell Death Differ. 2016;23:1542–54.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Rasola A, Neckers L, Picard D. Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells. Trends Cell Biol. 2014;24(8):455–63.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Saisawat P, Kohl S, Hilger AC, Hwang DY, Yung Gee H, Dworschak GC, Tasic V, Pennimpede T, Natarajan S, Sperry E, Matassa DS, Stajić N, Bogdanovic R, de Blaauw I, Marcelis CL, Wijers CH, Bartels E, Schmiedeke E, Schmidt D, Märzheuser S, Grasshoff-Derr S, Holland-Cunz S, Ludwig M, Nöthen MM, Draaken M, Brosens E, Heij H, Tibboel D, Herrmann BG, Solomon BD, de Klein A, van Rooij IA, Esposito F, Reutter HM, Hildebrandt F. Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. Kidney Int. 2014;85(6):1310–7.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Siegelin MD, Plescia J, Raskett CM, Gilbert CA, Ross AH, Altieri DC. Global targeting of subcellular heat shock protein-90 networks for therapy of glioblastoma. Mol Cancer Ther. 2010;9(6):1638–46.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB. Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem. 1995;270(8):3574–81.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Zhang B, Wang J, Huang Z, Wei P, Liu Y, Hao J, Zhao L, Zhang F, Tu Y, Wei T. Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer. Oncotarget. 2015;6(42):44495–508.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Dipartimento di Medicina Molecolare e Biotecnologie MedicheUniversità di Napoli “Federico II”NaplesItaly
  2. 2.Dipartimento di Scienze Mediche e ChirurgicheUniversità di Foggia/Laboratori di Ricerca Preclinica e Traslazionale, IRCCS, Centro di Riferimento Oncologico della BasilicataFoggiaItaly