Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: PPDPF suppresses the development of hepatocellular carcinoma through TRIM21-mediated ubiquitination of RIPK1

PROVIDER: PRJNA937032 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23606786_1.fastq.gz	Fastqsanger.gz
	SRR23606786_2.fastq.gz	Fastqsanger.gz
	SRR23606787_1.fastq.gz	Fastqsanger.gz
	SRR23606787_2.fastq.gz	Fastqsanger.gz
	SRR23606788_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

PPDPF suppresses the development of hepatocellular carcinoma through TRIM21-mediated ubiquitination of RIPK1

Project description:Our study have shown that PPDPF promoted NF-κB activation through TRIM21-mediated K63-linked ubiquitination of RIPK1 in hepatocytes. Upon TNF-α stimulation, PPDPF enhances TRIM21/RIPK1 interaction and increases TRIM21-mediated K63-linked ubiquitination of RIPK1, which promotes NF-κB activation.To map the ubiquitination site of RIPK1 regulated by PPDPF, we performed MS analysis using control and RIPK1-overexpressing HEK293T cells with or without PPDPF overexpression

2023-02-21 | PXD040301 |

MCM8 mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease

Project description:Mitophagy is a major quality control pathway that removes unwanted or dysfunctional mitochondria, and plays an essential role in vascular health. Here we show that MCM8 expression is significantly decreased in children with Kawasaki disease (KD) who developed coronary artery aneurysms. Mechanistically, we discover that nitric oxide (NO) signaling promotes TRIM21 mediated MCM8 ubiquitination, which disrupts its interaction with MCM9 and promotes its cytosolic export. In the cytosol, MCM8 relocates to the mitochondria pore forming proteins and promotes their ubiquitination by TRIM21. In addition, MCM8 directly recruits LC3 via its LIR motif and initiates mitophagy. This suppresses mitochondrial DNA-mediated activation of type I interferon via cGAS and STING. Mice that are deficient in Mcm8, Trim21, Nos2, or reconstituted with the East-Asian specific MCM8-P276 variant develop more severe coronary artery vasculopathy in the Lactobacillus casei extract-induced KD model. Collectively, the data suggest that MCM8 protects vascular health in the KD setting.

2023-06-29 | GSE235994 | GEO

Hepatocyte-Specific TAK1 Deficiency Drives RIPK1 Kinase-dependent Inflammation to Promote Liver Fibrosis and Hepatocellular Carcinoma

Project description:Transforming growth factor beta-activated kinase1 (TAK1) encoded by the gene MAP3K7 regulates multiple important downstream effectors involved in immune response, cell death and carcinogenesis. Hepatocyte-specific deletion of TAK1 in Tak1_Hep mice promotes liver fibrosis and hepatocellular carcinoma (HCC) formation. Here, we report that genetic inactivation of RIPK1 kinase using kinase dead knock-in D138N mutation in Tak1_Hep mice inhibits the expression of liver tumor biomarkers, liver fibrosis and HCC formation. Inhibition of RIPK1, however, has no or minimum effect on hepatocyte loss and compensatory proliferation, which are the recognized factors important for liver fibrosis and HCC development. Using single cell RNA-seq, we discover that inhibition of RIPK1 strongly suppresses inflammation induced by hepatocyte-specific loss of TAK1. Activation of RIPK1 promotes the transcription of key proinflammatory cytokines, such as CCL2, and CCR2+ macrophage infiltration. Our study demonstrates the role and mechanism of RIPK1 kinase in promoting inflammation, both cell-autonomously and cell-non-autonomously, in the development of liver fibrosis and HCC, independent of cell death and compensatory proliferation. We suggest the possibility of inhibiting RIPK1 kinase as a therapeutic strategy for reducing liver fibrosis and HCC development by inhibiting inflammation.

2020-07-08 | GSE148859 | GEO

METTL3 Confers Oxaliplatin Resistance Through the Activation of G6PD-enhanced Pentose Phosphate Pathway in Hepatocellular Carcinoma

Project description:Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m6A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mechanistically, METTL3 was found to modify E3 ligase TRIM21 near the 3'UTR with N6-methyladenosine, leading to reduced RNA stability upon recognition by YTHDF2. TRIM21, in turn, facilitated the degradation of the rate-limiting enzyme of PPP, G6PD, through the ubiquitination-proteasome pathway. Importantly, high expression of METTL3 was significantly associated with adverse prognosis and oxaliplatin resistance in HCC patients. Notably, treatment with the specific METTL3 inhibitor, STM2457, significantly improved the efficacy of oxaliplatin. These findings underscore the critical role of the METTL3/TRIM21/G6PD axis in driving oxaliplatin resistance and present a promising strategy to overcome chemoresistance in HCC.

2024-08-23 | GSE241802 | GEO

Proteomic analysis of TRAIL-induced endogenous RIPK3-dependent necrosome complex

Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.

2021-03-18 | PXD003383 | Pride

Modulation of proteostasis by the ubiquitin-conjugating enzyme UBE2N in immunoproteasome-positive AML

Project description:Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrate and ubiquitin linkages. In a screen for E2 dependencies in AML, UBE2N emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically-defective mouse model of UBE2N, revealing UBE2N's requirement in AML without significant impact on normal hematopoiesis. Unlike other E2s, which mediate Lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N exclusively synthesizes K63-linked chains, stabilizing or altering protein function. Proteomic analyses and a whole genome CRISPR-activation screen in pharmacologically and genetically UBE2N-inhibited AML cells unveiled a network of UBE2N-regulated oncoproteins. UBE2N inhibition reduced their protein levels, leading to increased K48-linked ubiquitination and degradation through the immunoproteasome and revealing UBE2N activity is enriched in immunoproteasome-positive AML. Furthermore, an interactome screen identified TRIM21 as the E3 ligase partnering with activated UBE2N in AML to modulate UBE2N-dependent proteostasis. In conclusion, UBE2N maintains proteostasis in AML by stabilizing oncoproteins through K63-linked ubiquitination and prevention of K48 ubiquitin-mediated degradation through the immunoproteasome. Thus, inhibition of UBE2N catalytic function suppresses leukemic cells through selective degradation of critical oncoproteins in immunoproteasome-positive AML.

2025-04-19 | GSE286041 | GEO

Hsa_circ_0098181 suppresses hepatocellular carcinoma through miR-18a-3p/PPARA axis

Project description:Hsa_circ_0098181 suppresses hepatocellular carcinoma through miR-18a-3p/PPARA axis

| PRJNA787228 | ENA

Galectin-9 suppresses growth of hepatocellular carcinoma in vitro

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in vitro study. Micro RNA expression of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed in vitro.

2015-03-01 | E-GEOD-55665 | biostudies-arrayexpress

Galectin-9 suppresses growth of hepatocellular carcinoma in vivo

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in xenograft model analysis. Micro RNA expression in xenografts of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed.

2015-03-01 | E-GEOD-55666 | biostudies-arrayexpress

Targeted Ubiquitination and Degradation of GOLM1 by CC-885 Suppresses Hepatocellular Carcinoma Growth and Metastasis

Project description:Targeted Ubiquitination and Degradation of GOLM1 by CC-885 Suppresses Hepatocellular Carcinoma Growth and Metastasis

| PRJNA1137341 | ENA