Apoptosis (London), 2008-03, Vol.13 (3), p.437-447
The HIPPI (HIP-1 protein interactor) protein is a multifunctional protein that is involved in the regulation of apoptosis. The interaction partners of HIPPI include HIP-1 (Huntingtin-interacting protein-1), Apoptin, Homer1c, Rybp/DEDAF, and BAR (bifunctional apoptosis regulator). In search for other binding partners of HIPPI, we performed a yeast two hybrid screen and identified BLOC1S2 (Biogenesis of lysosome-related organelles complex-1 subunit 2) as a novel HIPPI-interacting protein. In co-immunoprecipitation assays, BLOC1S2 specifically associates with HIPPI, but not with HIP-1. To study the expression of BLOC1S2 on the protein level, we generated a mouse monoclonal antibody specific for BLOC1S2 and a multiple tissue array comprising 70 normal and cancer tissue samples of diverse origin. BLOC1S2 protein is widely expressed in normal tissue as well as in malignant tumors with a tendency towards lower expression levels in certain subtypes of tumors. On the subcellular level, BLOC1S2 is expressed in an organellar-like pattern and co-localizes with mitochondria. Over-expression of BLOC1S2 in the presence or absence of HIPPI does not induce apoptosis. However, BLOC1S2 and HIPPI sensitize NCH89 glioblastoma cells to the pro-apoptotic actions of staurosporine and the death ligand TRAIL by enhancing caspase activation, cytochrome c release, and disruption of the mitochondrial membrane potential. Given its interaction with HIPPI and its pro-apoptotic activity, BLOC1S2 might play an important functional role in cancer and neurodegenerative diseases.
Biochemistry, general ; Mitochondria ; Biomedicine ; Lysosomes ; Oncology ; Cancer Research ; Huntington’s disease ; Virology ; Cell Biology ; Apoptosis ; Cancer ; Cilia ; Immunohistochemistry ; Apoptosis - drug effects ; Humans ; Caspase 3 - metabolism ; Caspase 8 - metabolism ; Molecular Sequence Data ; Male ; Membrane Potential, Mitochondrial - drug effects ; Tissue Distribution ; Adult ; Female ; Amino Acid Sequence ; Proteins - physiology ; Cytochromes c - secretion ; Mitochondria - metabolism ; Adaptor Proteins, Signal Transducing - physiology ; Sequence Alignment ; Animals ; TNF-Related Apoptosis-Inducing Ligand - physiology ; Glioblastoma - pathology ; Cell Line, Tumor ; Protein Binding ; HeLa Cells ; Neoplasms - pathology ; Staurosporine - pharmacology ; Glioblastoma multiforme ; Index Medicus
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