Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1041569 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To understand the activation of the MITF/TFE transcription factors in effective defense against pathogens we examined the genome wide distribution of TFE3 in control and activated mouse macrophages. It was determined that TFEB and TFE3 collaborate with each other to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of proinflammatory cytokines and key mediators of the inflammatory response. 4 samples were analyzed: Background Control, Control, Starvation, LPS
2016-02-01 | E-GEOD-75822 | biostudies-arrayexpress
Project description:To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. To understand the activation of the MITF/TFE transcription factors in response to ER stress we exposed mouse embryonic fibroblasts to starvation and tunicamycin (used to induce ER stress).
2016-02-01 | GSE75757 | GEO
Project description:To understand the activation of the MITF/TFE transcription factors in effective defense against pathogens we examined the genome wide distribution of TFE3 in control and activated mouse macrophages. It was determined that TFEB and TFE3 collaborate with each other to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of proinflammatory cytokines and key mediators of the inflammatory response.
2016-02-01 | GSE75822 | GEO
Project description:The activation of cellular quality control pathways to maintain metabolic homeostasis and mitigate diverse cellular stresses is emerging as a critical growth and survival mechanism in many cancers. Autophagy, a highly conserved cellular self-degradative process, is a key player in the initiation and maintenance of pancreatic ductal adenocarcinoma (PDA). However, the regulatory circuits that activate autophagy, and how they enable reprogramming of PDA cell metabolism are unknown. We now show that autophagy regulation in PDA occurs as part of a broader program that coordinates activation of lysosome biogenesis, function and nutrient scavenging, through constitutive activation of the MiT/TFE family of bHLH transcription factors. In PDA cells, the MiT/TFE proteins - MITF, TFE3 and TFEB - override a regulatory mechanism that controls their nuclear translocation, resulting in their constitutive activation. By orchestrating the expression of a coherent network of genes that induce high levels of lysosomal catabolic function, the MiT/TFE factors are required for proliferation and tumorigenicity of PDA cells. Importantly, unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular AA pools in PDA. This AA flux is part of a program that is essential for metabolic homeostasis and bioenergetics of PDA but not for their non-transformed counterparts. These results identify the MiT/TFE transcription factors as master regulators of the autophagy-lysosomal system in PDA and demonstrate a central role of the autophagosome-lysosome compartment in maintaining tumor cell metabolism through alternative amino acid acquisition and utilization. Examination of mRNA levels in pancreatic ductal adenocarcinoma (PDA) cell line 8988T after treatment with siRNA for control or TFE3
2015-04-03 | E-GEOD-62077 | biostudies-arrayexpress
Project description:The lysosomal function is down-regulated in the white prepupal fat body, resulting in the enlargement of lysosomes in the tissue. The enlargement is blocked by the forced activation of lysosomes by the overexpression of mitf, a sole homolog of the MiTF/TFE family transcription factors. Thus, it is possible to speculate that mitf participates in the down-regulation of lysosomes in the fat body. To test this possibility, we performed a comparative mRNA-seq of (1) wild-type white prepupal fat body, (2) mitf overexpressed white prepupal fat body, and (3) wild-type third instar larval fat body. First, a comparison of (1) and (2) showed that the overexpression of mitf upregulated transcription of most of the lysosome-related genes in the fat body, consistent with previous studies. Next, a comparison of (1) and (3) indicated that the transcription level of several lysosome-related genes was decreased in (1) compared to (3). However, most of the genes regulated by Mitf were not transcriptionally affected. These results suggest that mitf is dispensable for the downregulation of lysosomes in the white prepupal fat body.
2022-03-22 | GSE198690 | GEO
Project description:The activation of cellular quality control pathways to maintain metabolic homeostasis and mitigate diverse cellular stresses is emerging as a critical growth and survival mechanism in many cancers. Autophagy, a highly conserved cellular self-degradative process, is a key player in the initiation and maintenance of pancreatic ductal adenocarcinoma (PDA). However, the regulatory circuits that activate autophagy, and how they enable reprogramming of PDA cell metabolism are unknown. We now show that autophagy regulation in PDA occurs as part of a broader program that coordinates activation of lysosome biogenesis, function and nutrient scavenging, through constitutive activation of the MiT/TFE family of bHLH transcription factors. In PDA cells, the MiT/TFE proteins - MITF, TFE3 and TFEB - override a regulatory mechanism that controls their nuclear translocation, resulting in their constitutive activation. By orchestrating the expression of a coherent network of genes that induce high levels of lysosomal catabolic function, the MiT/TFE factors are required for proliferation and tumorigenicity of PDA cells. Importantly, unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosomal activation is specifically required to maintain intracellular AA pools in PDA. This AA flux is part of a program that is essential for metabolic homeostasis and bioenergetics of PDA but not for their non-transformed counterparts. These results identify the MiT/TFE transcription factors as master regulators of the autophagy-lysosomal system in PDA and demonstrate a central role of the autophagosome-lysosome compartment in maintaining tumor cell metabolism through alternative amino acid acquisition and utilization.
2015-04-03 | GSE62077 | GEO
Project description:Human prostate CWR22 OT-tumor cells were prospectively purified for expression of various stem cell markers (TRA-1-60/CD151/CD166/EpCAM/CD44/α2-Integrin). Unsorted total tumor cells or the additional marker positive cells that do not manifest stem-like characteristics were used as control. All these cells were subjected to molecular profiling of total RNA expression and the fold change data are tabulated according to S/TFE of the purified cells in relation to their control. Notes: Low S/TFE = Low sphere and tumor forming efficiency; Moderate S/TFE = Moderate sphere and tumor forming efficiency; High S/TFE = High sphere and tumor forming efficiency; FDR* = False Discovery Rate; FC = Fold Change; Signal = Average Expression Signal Level. Low-S/TFE, Moderate S/TFE, High S/TFE data sets were compared to No S/TFE control sets
2010-12-06 | E-GEOD-25690 | biostudies-arrayexpress
Project description:Human prostate CWR22 OT-tumor cells were prospectively purified for expression of various stem cell markers (TRA-1-60/CD151/CD166/EpCAM/CD44/α2-Integrin). Unsorted total tumor cells or the additional marker positive cells that do not manifest stem-like characteristics were used as control. All these cells were subjected to molecular profiling of total RNA expression and the fold change data are tabulated according to S/TFE of the purified cells in relation to their control. Notes: Low S/TFE = Low sphere and tumor forming efficiency; Moderate S/TFE = Moderate sphere and tumor forming efficiency; High S/TFE = High sphere and tumor forming efficiency; FDR* = False Discovery Rate; FC = Fold Change; Signal = Average Expression Signal Level. Low-S/TFE, Moderate S/TFE, High S/TFE data sets were compared to No S/TFE control sets
2010-12-06 | E-GEOD-25691 | biostudies-arrayexpress
Project description:Human prostate CWR22 OT-tumor cells were prospectively purified for expression of various stem cell markers (TRA-1-60/CD151/CD166/EpCAM/CD44/α2-Integrin). Unsorted total tumor cells or the additional marker positive cells that do not manifest stem-like characteristics were used as control. All these cells were subjected to molecular profiling of total RNA expression and the fold change data are tabulated according to S/TFE of the purified cells in relation to their control. Notes: Low S/TFE = Low sphere and tumor forming efficiency; Moderate S/TFE = Moderate sphere and tumor forming efficiency; High S/TFE = High sphere and tumor forming efficiency; FDR* = False Discovery Rate; FC = Fold Change; Signal = Average Expression Signal Level.
2010-12-06 | GSE25691 | GEO
Project description:The microphthalmia transcription factor Mitf has been shown to regulate B cell activation and tolerance. However, the underlying B cell-specific mechanisms responsible, and those that distinguish Mitf from closely related Mitf/TFE (MiT) transcription factors Tfe3, Tfeb, and Tfec, remain obscure. Two complementary mouse models of Mitf and MiT deficiency – the Mitfmi-vga9/mi-vga9 systemic loss-of-function mutation, and B-cell specific MiT family inactivation via transgenic expression of a trans-dominant negative (TDN) protein (TDN-B) – were used to identify MiT family candidate target genes and pathways. Both models displayed spontaneous splenomegaly coincident with elevated plasma cell numbers, autoantibody titers, and proteinuria. These abnormalities appeared dependent on T helper cells, but independent of other non-B cell intrinsic effects of systemic Mitf inactivation. MiT inactivation in B cells augmented aspects of lupus-like autoimmune disease on the C57BL/6-Faslpr/lpr background. In both models, RNAseq of ex vivo resting B cells showed transcriptional upregulation of genes that control cell cycle, germinal center responses, and plasma cell differentiation. Among the genes strongly upregulated in both models were Socs6, Isp53 (Baiap1), S1pR2, and IgG2b/c. Mitf null B cells, but not TDN-B cells, showed evidence of type I interferon dysregulation implicating non-autonomous B-lymphocyte mechanisms caused by systemic absence of Mitf. These studies clarify Mitf's role as 1) a key regulator of a B cell intrinsic germinal center program that influences self-tolerance through novel target genes, and 2) a regulator of systemic inflammatory processes that can impact the B cell microenvironment.
2024-01-10 | GSE252903 | GEO