The p53 tumor suppressor protein plays a crucial role in tumorigenesis by controlling cell-cycle progression and apoptosis. We have previously described a transcript designated tumor suppressor activated pathway-6 (TSAP6) that is up-regulated in the p53-inducible cell line, LTR6. Cloning of the murine and human fulllength TSAP6 cDNA revealed that it encodes a 488-aa protein with five to six transmembrane domains. This gene is the murine and human homologue of the recently published rat pHyde. Antibodies raised against murine and human TSAP6 recognize a 50-to 55-kDa band induced by p53. Analysis of the TSAP6 promoter identified a functional p53-responsive element. Functional studies demonstrated that TSAP6 antisense cDNA diminished levels of the 50-to 55-kDa protein and decreased significantly the levels of p53-induced apoptosis. Furthermore, TSAP6 small interfering RNA inhibited apoptosis in TSAP6-overexpressing cells. Yeast two-hybrid analysis followed by GST͞in vitro-transcribed͞translated pulldown assays and in vivo coimmunoprecipitations revealed that TSAP6 associated with Nix, a proapoptotic Bcl-2-related protein and the Myt1 kinase, a negative regulator of the G 2͞M transition. Moreover, TSAP6 enhanced the susceptibility of cells to apoptosis and cooperated with Nix to exacerbate this effect. Cell-cycle studies indicated that TSAP6 could augment Myt1 activity. Overall, these data suggest that TSAP6 may act downstream to p53 to interface apoptosis and cell-cycle progression.
Glucose transporter (GLUT) expression and regulation were studied in rat brain endothelial cells in primary culture (RBEC) and in immortalised RBE4 cells. Immunoblotting analysis showed a low expression of the endothelium-specific GLUT1 in RBEC and RBE4 cells compared to isolated brain capillaries. RBEC and RBE4 cells also expressed the GLUT3 isoform, whereas it was not present in isolated brain capillaries. No change in GLUT expression was observed in endothelial cells treated with astrocyte-conditioned medium. However, treatment with conditioned medium obtained from glucose-deprived astrocytes increased endothelial GLUT1 expression and glucose uptake. These results suggest that astrocytes submitted to hypoglycaemic conditions may release factor(s) that increase glucose uptake through the blood-brain barrier.
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