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The doppel gene biology: a scientific journey from brain to testis, and return.
No full textDoppel is a newly recognized prion-like molecule encoded by a novel gene locus, PRND,
located on the same chromosomal region of the prion (PRNP) coding gene. Doppel was considered
a paralogue and the first member of the prion-gene family, possibly originated through an ancestral
gene duplication event. Prion and doppel have different expression patterns, suggesting that the gene
products exhibit different biological functions. Actually, doppel is not involved in the aetiology of the
Transmissible Spongiform Encephalopathies (TSEs) or “prion diseases” and is highly expressed only
within the testicular tissue, suggesting an important physiological role in the process of spermatogenesis.
The restricted spatial and temporal expression profile of doppel has suggested its investigation within
particular pathological contexts, such as cancers, showing that it might represent a novel and attractive
diagnostic molecular marker and that might provide insights into the regulatory pathways of tumor-cell
transformation
Cell density modulates SHC3 expression and survival of human glioblastoma cells through Fak activation.
No full textPrion-like doppel gene (PRND): a new molecular marker potentially involved in leukemogenesis
No full textThe prion-like protein doppel (Dpl) interacts with the human receptor for activated C-Kinase 1 (RACK1) Protein
No full textBACKGROUND: Doppel (Dpl) is a homologue of the prion protein (PrPC). In contrast to PrP(C), Dpl is dispensable for prion disease, but appears to have an essential function in male spermatogenesis. Recently, Dpl has been found to be aberrantly expressed in astrocytic and leukaemic tumor specimens, showing a peculiar cytosolic cellular localization. The aim of this study was to clarify some of the putative Dpl interacting proteins. MATERIALS AND METHODS: A yeast two hybrid system was employed and the results were verified by co-immunoprecipitation using transfected cells. RESULTS: Several potential Dpl-binding candidates were identified and, among them, the receptor for activated C-kinase (RACK1) protein was further investigated. RACK1 deletion mutants showed that some of its WD containing domains were directly involved in the binding with Dpl. Our data showed that Dpl interacts with RACK1 by means of its structured globular carboxyl-terminal region. CONCLUSION: This new Dpl interacting partner might suggest functional hypotheses about the role of this protein in an astrocytoma context where Dpl was found ectopically expressed
Development of a Novel Bioinformatics Tool for In Silico Validation of Protein Interactions
Full text linkProtein interactions are crucial in most biological processes. Several in silico methods have been recently developed to predict them. This paper describes a bioinformatics method that combines sequence similarity and structural information to support experimental studies on protein interactions. Given a target protein, the approach selects the most likely interactors among the candidates revealed by experimental techniques, but not yet in vivo validated. The sequence and the structural information of the in vivo confirmed proteins and complexes are exploited to evaluate the candidate interactors. Finally, a score is calculated to suggest the most likely interactors of the target protein. As an example, we searched for GRB2 interactors. We ranked a set of 46 candidate interactors by the presented method. These candidates were then reduced to 21, through a score threshold chosen by means of a cross-validation strategy. Among them, the isoform 1 of MAPK14 was in silico confirmed as a GRB2 interactor. Finally, given a set of already confirmed interactors of GRB2, the accuracy and the precision of the approach were 75% and 86%, respectively. In conclusion, the proposed method can be conveniently exploited to select the proteins to be experimentally investigated within a set of potential interactors.</jats:p
Absence of interaction between doppel and GFAP, Grb2, PrPC proteins in human tumor astrocytic cells
No full textBACKGROUND: The doppel protein (Dpl) is a newly recognized cellular prion protein (PrP(C))-like molecule encoded by a novel gene locus, PRND, located on the same chromosomal region of the PrP(C) coding gene. Recently, Dpl was shown to be aberrantly expressed in astrocytic tumor specimens and in astrocytoma-derived cell lines, showing a peculiar cytoplasmic localization. Here, Dpl interactions with some of the prion-interacting proteins were studied. In particular, whether the tumor astrocytic environment is suitable for doppel interaction with GFAP and Grb2 proteins, as well as with the PrPC protein itself was investigated. MATERIALS AND METHODS: In order to verify our hypothesis, an innovative mammalian two-hybrid system and co-immunoprecipitation assays were employed. RESULTS: The results reported the absence of protein interactions. Our findings provided evidence that, in our astrocytoma cell-based model, Dpl does not share with PrP(C) the ability to interact with GFAP and Grb2. CONCLUSION: Identifying Dpl ligands may provide new insights into the involvement of Dpl in astrocytoma tumor progression
Silencing of cellular prion protein (PrPC) by antisense strategy induces autophagic cell death in human glial tumor cells
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