Browsing by Subject "transcriptional regulation"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Function and Regulation of the Natural Killer Cell Receptor 2B4 (CD244)(2005-05-01) Vaidya, Swapnil V.; Porunelloor A. Mathew; Richard Easom; Hriday DasThe purpose of these studies was to investigate two issues related to the natural killer (NK) cell receptor, 2B4 (CD244) – its in vivo function and transcriptional regulation. In previous in vitro studies, ligation of 2B4 with a monoclonal antibody enhanced the cytotoxicity of NK and CD8 T cells against various tumor cell lines, indicating that 2B4 is an activating receptor. To study the role of 2B4 in vivo, 2B4 deficient (2B4-/-) mice were used. The initial characterization of the 2B4-/- mice indicate a thymic developmental defect with an increase in the immature CD4-/CD8- population in the thyme of female but not male mice. NK cells from the 2B4-/- mice were impaired in activation by IL-2 as compared to wild type NK cells. These results suggest a role of 2B4 in lymphoid development. The in vivo role of 2B4 in tumor rejection was studied in a mouse tumor model in which melanoma cells were injected intravenously and pulmonary metastases enumerated 14 days later. The murine melanoma cell line, B16, was stably transfected with CD48, the counter-receptor for 2B4. Using CD48+ and CD48- B16 cells in tumor experiments indicated that 2B4 functioned as an inhibitory receptor. In addition, a gender-specific role of 2B4 in the rejection of B16 melanoma cells was discovered. 2B4-/- male mice cleared B16 cells more efficiently than wild type male mice, while female 2B4-/- mice were impaired in controlling tumor growth as compared to wild type female mice. In vitro and in vivo studies indicate a complex role for NK cells in the mechanism of this gender effect. Several studies have shown that the expression of 2B4 is upregulated during viral infections and under certain cytokine stimulation. Previously, it has been shown activator protein-1 (AP-1) plays an important role in the transcription of the 2B4 gene. In this study an Ets transcription factor was shown to upregulate the transcription of the gene. This element functions in an AP-1 dependent manner. Stimulation of surface 2B4 down-regulates its own expression by decreasing the activity of the Ets element in the 2B4 promoter. These studies identify a role of 2B4 in lymphoid development and tumor rejection in vivo. The gender-specific defect in 2B4 knock-out mice implicates its role in lupus. The transcriptional studies provide insights into the regulation of 2B4 gene.Item The Emerging Roles of mTORC1 in Macromanaging Autophagy(MDPI, 2019-09-24) Dossou, Akpedje; Basu, AlakanandaAutophagy is a process of self-degradation that enables the cell to survive when faced with starvation or stressful conditions. The mechanistic target of rapamycin (mTOR), also known as the mammalian target of rapamycin, plays a critical role in maintaining a balance between cellular anabolism and catabolism. mTOR complex 1 (mTORC1) was unveiled as a master regulator of autophagy since inhibition of mTORC1 was required to initiate the autophagy process. Evidence has emerged in recent years to indicate that mTORC1 also directly regulates the subsequent steps of the autophagy process, including the nucleation, autophagosome elongation, autophagosome maturation and termination. By phosphorylating select protein targets of the autophagy core machinery and/or their regulators, mTORC1 can alter their functions, increase their proteasomal degradation or modulate their acetylation status, which is a key switch of the autophagy process. Moreover, it phosphorylates and alters the subcellular localization of transcription factors to suppress the expression of genes needed for autophagosome formation and lysosome biogenesis. The purpose of this review article is to critically analyze current literatures to provide an integrated view of how mTORC1 regulates various steps of the autophagy process.