Browse
Submit Data
Databases
API
Help

Dataset Information

48 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth.

ABSTRACT: Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MARCH7 activated NFkB and Wnt/β-catenin pathways. Finally, MARCH7 was regulated by miR-101. Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.

SUBMITTER: Hu J

PROVIDER: S-EPMC4494930 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth.

Hu Jianguo J Meng Ying Y Yu Tinghe T Hu Lina L Mao Ming M

Oncotarget 20150501 14

Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MA ...[more]

PMID: 25895127

Similar Datasets

Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7.

Project description:The tumor suppressor p53 plays a prominent role in the protection against cancer. The activity of p53 is mainly controlled by the ubiquitin E3 ligase Mdm2, which targets p53 for proteasomal degradation. However, the regulation of Mdm2 remains not well understood. Here, we show that MARCH7, a RING domain-containing ubiquitin E3 ligase, physically interacts with Mdm2 and is essential for maintaining the stability of Mdm2. MARCH7 catalyzes Lys63-linked polyubiquitination of Mdm2, which impedes Mdm2 autoubiquitination and degradation, thereby leading to the stabilization of Mdm2. MARCH7 also promotes Mdm2-dependent polyubiquitination and degradation of p53. Furthermore, MARCH7 is able to regulate cell proliferation, DNA damage-induced apoptosis, and tumorigenesis via a p53-dependent mechanism. These findings uncover a novel mechanism for the regulation of Mdm2 and reveal MARCH7 as an important regulator of the Mdm2-p53 pathway.

| S-EPMC5797962 | biostudies-literature

The ubiquitin E3 ligase MARCH7 is differentially regulated by the deubiquitylating enzymes USP7 and USP9X.

Project description:Protein modification by one or more ubiquitin chains serves a critical signalling function across a wide range of cellular processes. Specificity within this system is conferred by ubiquitin E3 ligases, which target the substrates. Their activity is balanced by deubiquitylating enzymes (DUBs), which remove ubiquitin from both substrates and ligases. The RING-CH ligases were initially identified as viral immunoevasins involved in the downregulation of immunoreceptors. Their cellular orthologues, the Membrane-Associated RING-CH (MARCH) family represent a subgroup of the classical RING genes. Unlike their viral counterparts, the cellular RING-CH proteins appear highly regulated, and one of these in particular, MARCH7, was of interest because of a potential role in neuronal development and lymphocyte proliferation. Difficulties in detection and expression of this orphan ligase lead us to search for cellular cofactors involved in MARCH7 stability. In this study, we show that MARCH7 readily undergoes autoubiquitylation and associates with two deubiquitylating enzymes - ubiquitin-specific protease (USP)9X in the cytosol and USP7 in the nucleus. Exogenous expression and short interfering RNA depletion experiments demonstrate that MARCH7 can be stabilized by both USP9X and USP7, which deubiquitylate MARCH7 in the cytosol and nucleus, respectively. We therefore demonstrate compartment-specific regulation of this E3 ligase through recruitment of site-specific DUBs.

| S-EPMC3761688 | biostudies-literature

Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding.

Project description:Tau is the major microtubule-associated protein in neurons involved in microtubule stabilization in the axonal compartment. Changes in tau gene expression, alternative splicing and posttranslational modification regulate tau function and in tauopathies can result in tau mislocalization and dysfunction, causing tau aggregation and cell death. To uncover proteins involved in the development of tauopathies, a yeast two-hybrid system was used to screen for tau-interacting proteins. We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We defined the tau binding domain to amino acids 552-682 of axotrophin comprising the RING-variant domain. Co-immunoprecipitation and co-localization confirmed the specificity of the interaction. Intracellular localization of axotrophin is determined by an N-terminal nuclear targeting signal and a C-terminal nuclear export signal. In AD brain nuclear localization is lost and axotrophin is rather associated with neurofibrillary tangles. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. In vitro ubiquitination of four-repeat tau results in incorporation of up to four ubiquitin molecules compared to two molecules in three-repeat tau. In summary, we present a novel tau modification occurring preferentially on 4-repeat tau protein which modifies microtubule-binding and may impact on the pathogenesis of tauopathies.

| S-EPMC4311138 | biostudies-literature

Degradation of DRAK1 by CUL3/SPOP E3 Ubiquitin ligase promotes tumor growth of paclitaxel-resistant cervical cancer cells.

Project description:Despite favorable responses to initial chemotherapy, drug resistance is a major cause limiting chemotherapeutic efficacy in many advanced cancers. However, mechanisms that drive drug-specific resistance in chemotherapy for patients with advanced cancers are still unclear. Here, we report a unique role of death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK1) associated with paclitaxel resistance in cervical cancer cells. Interestingly, DRAK1 protein level was markedly decreased in paclitaxel-resistant cervical cancer cells without affecting its mRNA expression, which resulted in an increase in tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, as well as an activation of TRAF6-mediated nuclear factor-kappa B (NF-κB) signaling cascade, thereby promoting tumor progression. DRAK1 depletion markedly increased the chemotherapeutic IC50 values of paclitaxel in cervical cancer cells. Ectopic expression of DRAK1 inhibited growth of paclitaxel-resistant cervical cancer cells in vitro and in vivo. Furthermore, DRAK1 was markedly underexpressed in chemoresistant cervical cancer patient tissues compared with chemosensitive samples. We found that DRAK1 protein was destabilized through K48-linked polyubiquitination promoted by the Cullin scaffold protein 3 (CUL3) / speckle-type POZ (poxvirus and zinc finger protein) protein (SPOP) E3 ubiquitin ligase in paclitaxel-resistant cells. Collectively, these findings suggest that DRAK1 may serve as a potential predictive biomarker for overcoming paclitaxel resistance in cervical cancer.

| S-EPMC8863983 | biostudies-literature

The E3 Ubiquitin Ligase Peli1 Deficiency Promotes Atherosclerosis Progression.

Project description:BackgroundAtherosclerosis is a chronic inflammatory vascular disease and the main cause of death and morbidity. Emerging evidence suggests that ubiquitination plays an important role in the pathogenesis of atherosclerosis including control of vascular inflammation, vascular smooth muscle cell (VSMC) function and atherosclerotic plaque stability. Peli1 a type of E3 ubiquitin ligase has emerged as a critical regulator of innate and adaptive immunity, however, its role in atherosclerosis remains to be elucidated.MethodsApoe-/- mice and Peli1-deficient Apoe-/- Peli1-/- mice were subject to high cholesterol diet. Post sacrifice, serum was collected, and atherosclerotic plaque size and parameters of atherosclerotic plaque stability were evaluated. Immunoprofiling and foam cell quantification were performed.ResultsPeli1 deficiency does not affect atherosclerosis lesion burden and cholesterol levels, but promotes VSMCs foam cells formation, necrotic core expansion, collagen, and fibrous cap reduction. Apoe-/- Peli1-/- mice exhibit a storm of inflammatory cytokines, expansion of Th1, Th1, Th17, and Tfh cells, a decrease in regulatory T and B cells and induction of pro-atherogenic serum level of IgG2a and IgE.ConclusionsIn the present study, we uncover a crucial role for Peli1 in atherosclerosis as an important regulator of inflammation and VSMCs phenotypic modulation and subsequently atherosclerotic plaque destabilization.

| S-EPMC9265341 | biostudies-literature

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation.

Project description:The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain.

| S-EPMC6553684 | biostudies-literature

E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition.

Project description:In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

| S-EPMC7997893 | biostudies-literature

The E3 Ubiquitin Ligase TRIM21 Promotes HBV DNA Polymerase Degradation.

Project description:The tripartite motif (TRIM) protein family is an E3 ubiquitin ligase family. Recent reports have indicated that some TRIM proteins have antiviral functions, especially against retroviruses. However, most studies mainly focus on the relationship between TRIM21 and interferon or other antiviral effectors. The effect of TRIM21 on virus-encoded proteins remains unclear. In this study, we screened candidate interacting proteins of HBV DNA polymerase (Pol) by FLAG affinity purification and mass spectrometry assay and identified TRIM21 as its regulator. We used a coimmunoprecipitation (co-IP) assay to demonstrate that TRIM21 interacted with the TP domain of HBV DNA Pol. In addition, TRIM21 promoted the ubiquitination and degradation of HBV DNA Pol using its RING domain, which has E3 ubiquitin ligase activity. Lys260 and Lys283 of HBV DNA Pol were identified as targets for ubiquitination mediated by TRIM21. Finally, we uncovered that TRIM21 degrades HBV DNA Pol to restrict HBV DNA replication, and its SPRY domain is critical for this activity. Taken together, our results indicate that TRIM21 suppresses HBV DNA replication mainly by promoting the ubiquitination of HBV DNA Pol, which may provide a new potential target for the treatment of HBV.

| S-EPMC7150939 | biostudies-literature

Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase.

Project description:Necdin, a pleiotropic protein that promotes differentiation and survival of mammalian neurons, is a member of MAGE (melanoma antigen) family proteins that share a highly conserved MAGE homology domain. Several MAGE proteins interact with ubiquitin E3 ligases and modulate their activities. However, it remains unknown whether MAGE family proteins interact with SUMO (small ubiquitin-like modifier) E3 ligases such as PIAS (protein inhibitor of activated STAT) family, Nsmce2/Mms21 and Cbx4/Pc2. In the present study, we examined whether necdin interacts with these SUMO E3 ligases. Co-immunoprecipitation analysis revealed that necdin, MAGED1, MAGEF1 and MAGEL2 bound to PIAS1 but not to Nsmce2 or Cbx4. These SUMO E3 ligases bound to MAGEA1 but failed to interact with necdin-like 2/MAGEG1. Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination. Both PIAS1 and necdin were associated with the nuclear matrix, where the PIAS1 terminal deletion mutants failed to localize, implying that the nuclear matrix is indispensable for necdin-dependent ubiquitination of PIAS1. Our data suggest that necdin suppresses PIAS1 both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent degradation.

| S-EPMC4049815 | biostudies-literature

RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity.

Project description:Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment.

| S-EPMC10648572 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data