| Autor: |
AMOROSO, MARIA ROSARIA, MATASSA, DANILO SWANN, PALADINO, SIMONA, SARNATARO, DANIELA, GARBI, CORRADO, ESPOSITO, FRANCA, Laudiero G, Egorova AV, Polishchuk RS, Maddalena F, Piscazzi A, Landriscina M |
| Přispěvatelé: |
Amoroso, MARIA ROSARIA, Matassa, DANILO SWANN, Laudiero, G, Egorova, Av, Polishchuk, R, Maddalena, F, Piscazzi, A, Paladino, Simona, Sarnataro, Daniela, Garbi, Corrado, Landriscina, M, Esposito, Franca |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Popis: |
Tumor necrosis factor receptor-associated protein-1 (TRAP1) is a mitochondrial (MITO) antiapoptotic heat-shock protein. The information available on the TRAP1 pathway describes just a few well-characterized functions of this protein in mitochondria. However, our group's use of mass-spectrometric analysis identified TBP7, an AAA-ATPase of the 19S proteasomal subunit, as a putative TRAP1-interacting protein. Surprisingly, TRAP1 and TBP7 colocalize in the endoplasmic reticulum (ER), as demonstrated by biochemical and confocal/electron microscopic analyses, and interact directly, as confirmed by fluorescence resonance energy transfer analysis. This is the first demonstration of TRAP1's presence in this cellular compartment. TRAP1 silencing by short-hairpin RNAs, in cells exposed to thapsigargin-induced ER stress, correlates with upregulation of BiP/Grp78, thus suggesting a role of TRAP1 in the refolding of damaged proteins and in ER stress protection. Consistently, TRAP1 and/or TBP7 interference enhanced stress-induced cell death and increased intracellular protein ubiquitination. These experiments led us to hypothesize an involvement of TRAP1 in protein quality control for mistargeted/misfolded mitochondria-destined proteins, through interaction with the regulatory proteasome protein TBP7. Remarkably, expression of specific MITO proteins decreased upon TRAP1 interference as a consequence of increased ubiquitination. The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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