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Physiological role of the peripheral benzodiazepine receptor and its implications in apoptotic cell-death signaling pathways (PBR AND APOPTOSIS)
Start date: 03 Mar 2008, End date: 02 Mar 2009 PROJECT  FINISHED 

The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein receptor, mainly found on the outer mitochondrial membrane of cells. The PBR seems to play a role in several cellular functions, including heme synthesis, steroidogenesis, DNA synthesis, cell growth and differentiation.Recently, a role for PBR in apoptosis has also been proposed and a number of findings argue in favour of this:- over-expression of PBR has been described in a large range of human cancers;- regulation of programmed cell death has in mitochondria a check-point targeted by various conventional cancer therapies; and- PBR ligation by directed drugs, enhances apoptosis induction in many types of tumours, reversing the Bcl-2 cytoprotective effects.These findings promoted the development of PBR targeting approaches in treatment of human cancers. Even though experimental data suggest that PBR may play a key role in various physiological and pathological processes, very little data are available on the protein-receptor cell physiology and on its role in apoptotic cell-death signalling pathways.OBJECTIVES: Our aim is then to investigate these aspects, studying the PBR capacity to modulate and shape the cell signalling, principally in respect of the mitochondrial function.In detail, we will:- examine the PBR expression and localization in cells of interest;- generate by molecular biology techniques recombinant probes of PBR;- investigate the result on cell signalling pathways of the PBR genetically and pharmacologically modulation;- finally, asses PBR role in respect of the apoptotic cell death and tumourigenesis.
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