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Targeted Vpr-derived peptides reach mitochondria to induce apoptosis of αVβ3-expressing endothelial cells.
- Source :
- Cell Death & Differentiation; Mar2007, Vol. 14 Issue 3, p422-435, 14p, 8 Graphs
- Publication Year :
- 2007
-
Abstract
- The HIV-1 encoded apoptogenic protein Vpr induces mitochondrial membrane permeabilization (MMP) via interactions with the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocator (ANT). We have designed a peptide, TEAM-VP, composed of two functional domains, one a tumor blood vessel RGD-like ‘homing’ motif and the other an MMP-inducing sequence derived from Vpr. When added to isolated mitochondria, TEAM-VP interacts with ANT and VDAC, reduces oxygen consumption and overcomes Bcl-2 protection to cause inner and outer MMP. TEAM-VP specifically recognizes cell-surface expressed α<subscript>V</subscript>β<subscript>3</subscript> integrins, internalizes, temporarily localizes to lysosomes and progressively co-distributes with the mitochondrial compartment with no sign of lysosomal membrane permeabilization. Finally TEAM-VP reaches mitochondria of angiogenic endothelial cells to induce mitochondrial fission, dissipation of the mitochondrial transmembrane potential (ΔΨ<subscript>m</subscript>), cytochrome c release and apoptosis hallmarks. Hence, this chimeric peptide constitutes the first example of a virus-derived mitochondriotoxic compound as a candidate to kill selectively tumor neo-endothelia.Cell Death and Differentiation (2007) 14, 422–435. doi:10.1038/sj.cdd.4402018; published online 4 August 2006 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 14
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 24002701
- Full Text :
- https://doi.org/10.1038/sj.cdd.4402018