| 1. |
- Borsics, Tamas, et al.
(författare)
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Subcellular distribution and expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in malignant glioma : Influence on cell survival and migration
- 2010
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 101:7, s. 1624-1631
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Tidskriftsartikel (refereegranskat)abstract
- Our previous studies revealed that the expression of the 19-kDa protein prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is elevated in cancer tissues of the breast, colon, lung, and ovary, when compared to noncancerous tissues of paired samples. PRAF2 mRNA expression also correlated with several genetic and clinical features and is a candidate prognostic marker in the pediatric cancer neuroblastoma. The PRAF2-related proteins, PRAF1 and PRAF3, play multiple roles in cellular processes, including endo/exocytic vesicle trafficking and glutamate uptake. PRAF2 shares a high sequence homology with these family members, but its function remains unknown. In this study, we examined PRAF2 mRNA and protein expression in 20 different human cancer types using Affymetrix microarray and human tissue microarray (TMA) analyses, respectively. In addition, we investigated the subcellular distribution of PRAF2 by immunofluorescence microscopy and cell fractionation studies. PRAF2 mRNA and protein expression was elevated in several cancer tissues with highest levels in malignant glioma. At the molecular level, we detected native PRAF2 in small, vesicle-like structures throughout the cytoplasm as well as in and around cell nuclei of U-87 malignant glioma cells. We further found that monomeric and dimeric forms of PRAF2 are associated with different cell compartments, suggesting possible functional differences. Importantly, PRAF2 down-regulation by RNA interference significantly reduced the cell viability, migration, and invasiveness of U-87 cells. This study shows that PRAF2 expression is elevated in various tumors with exceptionally high expression in malignant gliomas, and PRAF2 therefore presents a candidate molecular target for therapeutic intervention. (Cancer Sci 2010).
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| 2. |
- Koomoa, Dana-Lynn T., et al.
(författare)
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Expression profile of PRAF2 in the human brain and enrichment in synaptic vesicles
- 2008
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 436:2, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- PRA1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with a prenylated Rab acceptor 1 (PRA1) motif and four transmembrane domains. Our previous studies revealed that PRAF2 is highly expressed in the brain and serves as a candidate prognostic marker in neuroblastoma (NB). PRAF2 is related to proteins PRAF1 (PRA1, prenylin, Yip3) and PRAF3 (GTRAP3-18, JWA, Arl6-IP5), both of which are enriched in the brain and implicated in cellular transport and endo/exocytic vesicle trafficking. However, the function for PRAF2 remains unknown. In this study, we analyzed the distribution and localization of PRAF2 in the mature human brain using two new antibodies specific for the protein. Analysis by immunohistochemistry revealed that in the human cerebellum, the PRAF2 protein was strongly expressed in Purkinje cells and, more moderately, in cells of the molecular and the granular layers. In the cerebral cortex, hippocampus, and lateral ventricles, PRAF2 protein was detected in neuronal cells, but not in non-neuronal cells. Intriguingly, immunoblot analysis revealed that PRAF2 is enriched in synaptic vesicles (SVs) prepared from rat brains. The expression of PRAF2 in specific regions of the brain including SVs suggest an important physiological function for this novel protein, possibly by participating in multiple aspects of SV maturation, transport, and signal transmission.
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