Proteome-wide identification of Hsc70 clients in autophagy altered K-Ras G12V MEFs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus (mouse)
SUBMITTER: Dr. Amit Kumar
PROVIDER: PXD029905 | JPOST Repository | Fri Nov 25 00:00:00 GMT 2022
REPOSITORIES: jPOST
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Individual.pdStudy | Other | |||
| Individual.pdStudy.bak | Other | |||
| S1_1.msf | Msf | |||
| S1_1.msfView | Msf | |||
| S1_1.pdResult | Other |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Drosophila Orb, the homologue of vertebrate CPEB is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb has also an essential function during early oogenesis which has not been addressed at the molecular level. Here, we show that orb prevents cell death during early oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy, by directly repressing, together with the CCR4 deadenylase, the translation of Autophagy-specific gene 12 (Atg12) mRNA. Autophagy and cell death observed in orb mutant ovaries are reduced by decreasing Atg12 or other Atg mRNA levels. These results reveal a role of Orb in translational repression and identify autophagy as an essential pathway regulated by Orb during early oogenesis. Importantly, they also establish translational regulation as a major mode of control of autophagy, a key process in cell homeostasis in response to environmental cues. Orb RIP-chip vs mock IP on ovaries from newly eclosed females.
2016-07-03 | E-GEOD-74474 | biostudies-arrayexpress
Project description:Drosophila Orb, the homologue of vertebrate CPEB is a key translational regulator involved in oocyte polarity and maturation through poly(A) tail elongation of specific mRNAs. orb has also an essential function during early oogenesis which has not been addressed at the molecular level. Here, we show that orb prevents cell death during early oogenesis, thus allowing oogenesis to progress. It does so through the repression of autophagy, by directly repressing, together with the CCR4 deadenylase, the translation of Autophagy-specific gene 12 (Atg12) mRNA. Autophagy and cell death observed in orb mutant ovaries are reduced by decreasing Atg12 or other Atg mRNA levels. These results reveal a role of Orb in translational repression and identify autophagy as an essential pathway regulated by Orb during early oogenesis. Importantly, they also establish translational regulation as a major mode of control of autophagy, a key process in cell homeostasis in response to environmental cues. Orb RIP-chip vs mock IP on ovaries from mature 3-5 day old females.
2016-07-03 | E-GEOD-74475 | biostudies-arrayexpress
Project description:During tumor growth-when nutrient and anabolic demands are high-autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster. Micro-computed X-ray tomography and metabolic profiling reveal that Ras<sup>V12</sup> ; scrib<sup>-/-</sup> tumors grow 10-fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, -motility, -feeding, and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.
2021-09-24 | MTBLS2771 | MetaboLights
Project description:Targeting protein for Xklp2 (TPX2) is a mitotic regulator frequently overexpressed in lung adenocarcinoma (LUAD), while its role in cancer stemness and autophagy remains incompletely understood. In this study, integrative bioinformatic analyses based on TCGA and GTEx datasets revealed that TPX2 overexpression in LUAD was associated with poor prognosis, elevated stemness scores, and increased expression of cancer stem cell-related markers. To investigate the molecular mechanisms underlying TPX2-mediated regulation in LUAD, RNA sequencing was performed in PC9 cells following TPX2 knockdown. Transcriptomic profiling and pathway analyses identified significant alterations in autophagy-related signaling pathways. In parallel, co-immunoprecipitation coupled with mass spectrometry (IP-MS) was conducted to characterize TPX2-associated protein interactions and explore potential regulatory networks involved in autophagy. Functional experiments further demonstrated that TPX2 depletion impaired autophagic flux and reduced stemness-associated phenotypes in LUAD cells, whereas TPX2 overexpression exerted opposite effects. These data provide transcriptomic and proteomic resources for investigating the role of TPX2-mediated autophagy in LUAD progression and cancer stemness.
2026-05-28 | GSE333531 | GEO
Project description:Nano gold simulated autophagy prevents cell death
| PRJNA542349 | ENA
Project description:The M6A modification plays an important role in the pathogenesis of various myeloid malignancies. However, its specific role in RAS mutant-induced myeloid malignancy is incompletely understood. In this study, we found that m6A methyltransferase METTL14 was highly expressed and associated with a shorter survival in a RAS-mutant myeloid malignancy, juvenile myelomonocytic leukemia (JMML). The knockout of METTL14 was revealed to significantly promote hematopoietic stem/progenitor cells (HSPCs) expansion and suppresses disease progression in a KrasG12D/+ mutant-induced mouse model of JMML. Moreover, knockout of METTL14 reduces hyperproliferation of KrasG12D/+ HSPCs and suppresses oncogenic KrasG12D/+-induced myeloid disease in a cell-autonomous manner. Mechanistically, we revealed that the knockout of METTL14 reduced the autophagy levels of HSPCs by suppressing the transcription and translation of autophagy-related genes, such as Atg5 and Atg9a, through m6A modification. Furthermore, we found that the autophagy inhibition through knockout of ATG5 in Kras mutant mice promoted the expansion of HSPCs and inhibited the progression of leukemia disease, consistent with the phenotypes of knockout of METTL14. Finally, we observed that combined treatment with an m6A inhibitor and a MEK inhibitor synergistically suppressed JMML growth. Collectively, these findings highlight the critical role of METTL14 in JMML tumorigenesis and suggest that m6A RNA modification represents a promising therapeutic target for this disease.
2026-01-21 | GSE298134 | GEO
Project description:Autophagy is a catabolic membrane trafficking process involved in degradation of cellular constituents through lysosomes, which maintains cell and tissue homeostasis. While much attention has been focused on autophagic turnover of cytoplasmic materials, little is known regarding the role of autophagy in degrading nuclear components. Here we report that autophagy machinery mediates degradation of nuclear lamina in mammalian cells, a process we term laminophagy. The autophagy protein LC3 is present in the nucleus and directly interacts with the nuclear lamina protein Lamin B1, and associates with lamin-associated domains (LADs) on chromatin. This interaction does not downregulate Lamin B1 during starvation, but mediates nuclear lamina degradation upon tumorigenic insults, such as by oncogenic Ras. Laminophagy is achieved by nucleus-to-cytosol transport that delivers Lamin B1 to lysosome for degradation. Inhibiting autophagy or LC3-Lamin B1 interaction prevents oncogenic Ras-induced Lamin B1 loss and delays oncogene-induced cell cycle arrest. Our study unveils a role of autophagy in degrading nuclear materials, and suggests laminophagy as a guarding mechanism protecting cells from tumorigenesis.
2015-10-08 | GSE63440 | GEO
Project description:The M6A modification plays an important role in the pathogenesis of various myeloid malignancies. However, its specific role in RAS mutant-induced myeloid malignancy is incompletely understood. In this study, we found that m6A methyltransferase METTL14 was highly expressed and associated with a shorter survival in a RAS-mutant myeloid malignancy, juvenile myelomonocytic leukemia (JMML). The knockout of METTL14 was revealed to significantly promote hematopoietic stem/progenitor cells (HSPCs) expansion and suppresses disease progression in a KrasG12D/+ mutant-induced mouse model of JMML. Moreover, knockout of METTL14 reduces hyperproliferation of KrasG12D/+ HSPCs and suppresses oncogenic KrasG12D/+-induced myeloid disease in a cell-autonomous manner. Mechanistically, we revealed that the knockout of METTL14 reduced the autophagy levels of HSPCs by suppressing the transcription and translation of autophagy-related genes, such as Atg5 and Atg9a, through m6A modification. Furthermore, we found that the autophagy inhibition through knockout of ATG5 in Kras mutant mice promoted the expansion of HSPCs and inhibited the progression of leukemia disease, consistent with the phenotypes of knockout of METTL14. Finally, we observed that combined treatment with an m6A inhibitor and a MEK inhibitor synergistically suppressed JMML growth. Collectively, these findings highlight the critical role of METTL14 in JMML tumorigenesis and suggest that m6A RNA modification represents a promising therapeutic target for this disease.
2026-01-21 | GSE298142 | GEO
Project description:RNASeq of Autophagy Mutant BMDMs
| PRJNA849244 | ENA