| http://purl.uniprot.org/citations/20388708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20388708 | http://www.w3.org/2000/01/rdf-schema#comment | "The cytoplasm and the nucleus have been identified as activity sites for granzyme B (GrB) following its delivery from cytotoxic lymphocyte granules into target cells. Here we report on the ability of exogenous GrB to insert into and function within a proteinase K-resistant mitochondrial compartment. We identified Hax-1 (HS-1-associated protein X-1), a mitochondrial protein involved in the maintenance of mitochondrial membrane potential, as a GrB substrate within the mitochondrion. GrB cleaves Hax-1 into two major fragments: an N-terminal fragment that localizes to mitochondria and a C-terminal fragment that localizes to the cytosol after being released from GrB-treated mitochondria. The N-terminal Hax-1 fragment major cellular impact is on the regulation of mitochondrial polarization. Overexpression of wild-type Hax-1 or its uncleavable mutant form protects the mitochondria against GrB or valinomycin-mediated depolarization. The N-terminal Hax-1 fragment functions as a dominant negative form of Hax-1, mediating mitochondrial depolarization in a cyclophilin D-dependent manner. Thus, induced expression of the N-terminal Hax-1 fragment results in mitochondrial depolarization and subsequent lysosomal degradation of such altered mitochondria. This study is the first to demonstrate GrB activity within the mitochondrion and to identify Hax-1 cleavage as a novel mechanism for GrB-mediated mitochondrial depolarization."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.086587"xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Hou W."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Han J."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Watkins S.C."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Goldstein L.A."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Rabinowich H."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/author | "Froelich C.J."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/pages | "22461-22472"xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/title | "Deregulation of mitochondrial membrane potential by mitochondrial insertion of granzyme B and direct Hax-1 cleavage."xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/20388708 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20388708 |
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