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TFEB promotes prostate cancer progression via regulating ABCA2-dependent lysosomal biogenesis

ABSTRACT: The goals of this study is to find effect of overexpression-TFEB in prostate cancer cell (DU145 cell line).

ORGANISM(S): Homo sapiens

PROVIDER: GSE163761 | GEO | 2021/02/25

REPOSITORIES: GEO

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TFEB promotes prostate cancer progression via regulating ABCA2-dependent lysosomal biogenesis

Project description:TFEB promotes prostate cancer progression via regulating ABCA2-dependent lysosomal biogenesis

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TFEB Promotes Prostate Cancer Progression <i>via</i> Regulating ABCA2-Dependent Lysosomal Biogenesis.

Project description: Not available

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TFEB-driven lysosomal biogenesis is pivotal for PGC1a-dependent renal stress resistance

Project description:Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is somewhat paradoxical that proliferator gamma coactivator 1-alpha (PGC1a), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1a’s induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1a knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1a not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1a did not consistent affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1a in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1a’s exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance.

2019-06-10 | GSE126259 | GEO

TFEB links autophagy to lysosomal biogenesis.

Project description: Not available

| S-EPMC3638014 | biostudies-literature

Mitochondrial energetic stress triggers AMPK/FNIP1-dependent TFEB nuclear translocation, inducing transcriptional waves of lysosomal and mitochondrial biogenesis.

Project description:Cells respond to mitochondrial energetic stress with rapid activation of the AMP-activated protein kinase (AMPK), which acutely inhibits anabolism and stimulates catabolism. AMPK also induces sustained transcriptional reprogramming of metabolism. The TFEB transcription factor is a major effector of AMPK signals, inducing lysosome genes following energetic stress. Yet the molecular mechanism underlying how AMPK activates TFEB remains unresolved. We demonstrate here that AMPK directly phosphorylates five conserved serine residues in FNIP1, which suppresses the function of the FLCN/FNIP1 RagC GAP complex, in turn controlling TFEB lysosomal localization. We demonstrate that FNIP1 phosphorylation is required for AMPK to induce nuclear translocation of TFEB, which is fully separable from AMPK control of canonical mTORC1 signaling. Using a non-phosphorylatable allele of FNIP1, we show that in parallel to lysosomal biogenesis, AMPK induces mitochondrial biogenesis via TFEB-dependent induction of PGC1a mRNA. This signaling from mitochondrial stress is also independent of amino-acid control of the Rags and TFEB, which still proceed normally in cells bearing the AMPK-non phosphorylatable allele of FNIP1. Taken together, mitochondrial energetic stress triggers AMPK/FNIP1-dependent TFEB nuclear translocation, inducing transcriptional waves of lysosomal and mitochondrial biogenesis.

2023-05-08 | GSE218827 | GEO

The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis [RNA-seq: 7dpf_liver]

Project description:Under homeostatic conditions, NRF2 is repressed by Kelch-like ECH-associated protein 1 (KEAP1). Here, we demonstrate that Keap1 deficiency induces Nrf2 activation and post-developmental lethality in zebrafish larvae. Loss of viability is preceded by severe liver abnormalities characterized by an accumulation of lysosomes. Mechanistically, we demonstrate that loss of Keap1 promotes aberrant activation of transcription factor EB (TFEB)/transcription factor binding to IGHM Enhancer 3 (TFE3)-dependent lysosomal biogenesis. Importantly, we find that NRF2-dependent regulation of lysosomal biogenesis is cell autonomous and evolutionarily conserved.

2023-04-30 | GSE230610 | GEO

The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis [RNA-seq: 7dpf_larvae]

2023-04-30 | GSE230607 | GEO

Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity

Project description:To identify the interaction proteins of TFEB, HEK293T cells transiently expressing TFEB-Flag were immunoprecipitated with anti-Flag beads. The beeds were used to do a LC/MS.

2024-03-13 | PXD050578 |

ATG conjugation system -dependent and -independent mechanisms underlie lysosomal stress-induced TFEB regulation

Project description:Transcription factor EB (TFEB), well characterized as a master regulator of autophagy and lysosomal biogenesis, is translocated to the nucleus and activated by varieties of cellular stresses including starvation and lysosomal damage. However, compared to the starvation condition, the molecular mechanism of TFEB activation by other stress conditions is poorly understood. Previously, we have shown that TFEB activation during lysosomal damage but not starvation condition depends on a subset of autophagy regulators, collectively called ATG conjugation system, whose function is essential for the lipidation of ATG8 proteins. In this study, by time-lapse imaging, we newly identified the presence of ATG conjugation system -independent TFEB regulation which precedes the ATG conjugation system-dependent regulation, designated mode I and mode II, respectively. Consistent with the presence of different modes, our time course transcriptome analysis revealed two different sets of TFEB downstream. Comprehensive interactome analysis of TFEB and subsequent functional screening identified unique regulars of TFEB in each mode: APEX1 for Mode I and CCT7 and/or TRIP6 for Mode II, respectively. APEX1 interacted with TFEB and was required for its protein stability in a manner independent of ATG conjugation system. On the other hand, both CCT7 and TRIP6 were accumulated on lysosomes during lysosomal damage and interacted with TFEB mainly in ATG conjugation system deficient cells, presumably blocking TFEB nuclear translocation. Moreover, we further revealed that TFEB regulatory mechanisms by other cellular stresses such as oxidative stress, proteasome inhibition, mitochondria depolarization, and DNA damage can be classified into either APEX1-mediated Mode I or TRIP6-mediated Mode II. Our results pave the way for a unified understanding TFEB regulatory mechanisms from the perspective of ATG conjugation system under varieties of cellular stresses.

2025-01-31 | GSE235340 | GEO

The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis

Project description:The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis

| PRJNA961964 | ENA