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Physiological role of the peripheral benzodiazepine receptor and its implications in apoptotic cell-death signaling pathways

Objective

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.

Field of science

  • /natural sciences/biological sciences/molecular biology
  • /natural sciences/biological sciences/cell biology/cell signaling
  • /medical and health sciences/clinical medicine/cancer

Call for proposal

FP6-2004-MOBILITY-11
See other projects for this call

Funding Scheme

ERG - Marie Curie actions-European Re-integration Grants

Coordinator

DEPARTMENT OF EXPERIMENTAL AND DIAGNOSTIC MEDICINE UNIVERSITY OF FERRARA, ITALY
Address
Via L.borsari 46
Ferrara
Italy