Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BAG2 inhibits the proliferation and migration of cervical cancer by slowing the degradation of STING

ABSTRACT: The fourth most prevalent illness in the world among women, cervical cancer has significant negative effects on both health and the economy in addition to high rates of morbidity and death. Understanding its molecular basis to guide clinical management is critical. STING, an innate immune sensor that induces type I interferon, plays a key role in enhancing anti-tumor activity. Despite the growing interest in the role played by STING in cervical cancer, the homeostatic regulatory mechanisms of STING in cervical cancer remain unknown. Here, we found that the BAG2-STUB1 complex regulates ubiquitin proteasomal degradation of STING, which affects the development of cervical cancer. Mechanistically, BAG2 inhibits ubiquitination of STING and stabilizes it by interacting with STING. Specifically, BAG2 inhibits STUB1 from linking the K48-conjugated ubiquitin chains at K338 and K370 of STING by forming a complex with STUB1. Functionally, upregulation of BAG2 expression could inhibit cervical cancer progression by activating the type I interferon response in a STING-dependent manner. Importantly, clinical cervical cancer samples showed a positive correlation between BAG2 and STING expression, and low BAG2 expression was strongly associated with clinical progression and poor prognosis in cervical cancer. Together, these findings describe the molecular mechanism by which the BAG2-STUB1 complex mediates the homeostatic regulation of STING, highlighting the important potential role of BAG2 in the diagnosis and treatment of cervical cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279947 | GEO | 2025/08/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity [RNAseq_STUB1KO]

Project description:In vivo CRISPR screens in CD8+ T cells have previously uncovered targets for cancer immunotherapy, yet they have not been used to compare the key regulators important at different stages of CD8+ T cell activation. Here we present two 899-gene in vivo CRISPR screens using naive or activated CD8+ T cells to address this gap. These screens identified the E3 ubiquitin ligase STUB1 as a novel negative regulator of anti-tumor CD8+ T cells. Stub1 knockout (KO) CD8+ T cells control tumor growth across multiple murine models. Mechanistically, STUB1 interacts with the adapter protein CHIC2 to regulate cytokine receptor expression in mouse and human CD8+ T cells. Among the cytokine receptors regulated by this complex, IL-27Ra is essential for Stub1/Chic2 KO-mediated tumor growth control. Together, these findings establish that the STUB1-CHIC2 complex as a novel regulator of cytokine receptor expression in CD8+ T cells and provide rationale for inhibiting this pathway to enhance CD8+ T cell-mediated anti-tumor immunity.

2025-06-10 | GSE294202 | GEO

Running Title: STUB1 regulates YTHDF1 stability and suppresses tumorigenesis of renal cell carcinomas

Project description:STIP1 homology and U-box protein 1 (STUB1), a key RING family E3 ubiquitin ligase, plays both oncogenic and tumor-suppressive roles in a variety of human cancers. However, the role and mechanism of STUB1 in clear cell renal cell carcinoma (ccRCC) remains poorly defined. Here, we identified YTHDF1 as a novel STUB1 interactor by affinity purification mass spectrometry (AP-MS). STUB1 polyubiquitylates YTHDF1 and promotes YTHDF1 degradation. STUB1 depletion stabilizes YTHDF1 in renal cancer cells. STUB1-knockdown renal cancer cells exhibit increased migration and invasion in YTHDF1 dependent manner. Further study demonstrates that STUB1 knockdown promoted the tumorigenicity of ccRCC in a xenograft model. Clinically, STUB1 expression is down-regulated in ccRCC tissues, and the low expression level of STUB1 was associated with higher tumor stage and poor overall survival in patients with ccRCC. These findings reveal that STUB1 acts as an E3 ubiquitin ligase and promotes degradation of YTHDF1, and STUB1 inhibits the tumorigenicity of ccRCC through ubiquitinating YTHDF1.

2023-10-07 | PXD045954 |

A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity

Project description:In vivo CRISPR screens using activated CD8+ T cells have uncovered novel immunotherapy targets for cancer, yet similar high-throughput screens have not been performed using naive CD8+ T cells. Here we present an 899-gene in vivo CRISPR screen using naive CD8+ T cells, which identified the E3 ubiquitin ligase STUB1 as a novel negative regulator of anti-tumor CD8+ T cell responses. Stub1 knockout (KO) CD8+ T cells control tumor growth across multiple murine models. Mechanistically, STUB1 interacts with the adapter protein CHIC2 to regulate IL-27Rα expression in mouse and human CD8+ T cells. IL-27Rα expression is essential for the accumulation of Stub1 KO or Chic2 KO CD8+ T cells in tumors and tumor growth control. Together, these findings demonstrate that the STUB1-CHIC2 complex is a novel regulator of cytokine receptor expression in CD8+ T cells and provide the rationale for inhibiting this pathway to improve CD8+ T cell-mediated anti-tumor immunity.

2025-06-10 | GSE265929 | GEO

Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer (Affymetrix)

Project description:Constitutively active androgen receptor (AR) signaling confers resistance to AR-targeted therapies. Here we show that the ubiquitin-mediated proteolysis pathway plays a critical role in the degradation of AR and its variants, particularly variant 7 (AR-V7). AR/AR-V7 proteinhomeostasis (proteostasis) requires interaction of the E3 ubiquitin ligase STUB1 and HSP70complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 reduces AR/AR-V7 expression which significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason scores prostate tumors. Our results reveal a novel mechanism of AR-V7 modulation via proteostasis which could be targeted to reduce AR-V7 expression and overcome resistance to AR-targeted therapies.

2018-10-05 | GSE120005 | GEO

Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer (RNA-Seq)

2018-10-05 | GSE120004 | GEO

STUB1 regulates antiviral RNAi through inducing ubiquitination and degradation of Dicer and AGO2 in mammals

Project description:RNA interference (RNAi) is a cell-intrinsic antiviral defense conserved in diverse organisms. However, the mechanism by which mammalian antiviral RNAi is regulated is largely unknown. Herein, we uncover that STUB1, an E3 ubiquitin ligase, interacts with and ubiquitinates AGO2, the core component of RNAi pathway, resulting in the degradation of AGO2 via ubiquitin-proteasome system. Additionally, STUB1 can induce the degradation of the other mammalian AGO proteins including AGO1, AGO3, and AGO4. Our further study reveals that STUB1 also interacts with and mediates the ubiquitination of Dicer, the endoribonuclease responsible for siRNA or miRNA biogenesis, via K48-linked poly-ubiquitin, which induces the degradation of Dicer and its specialized form, termed antiviral Dicer (aviDicer) that usually expresses in stem cells. Loss of STUB1 upregulated Dicer and AGO2, thereby enhancing antiviral RNAi to effectively inhibit viral RNA replication in mammalian cells. In vivo, the STUB1 deficiency markedly enhanced the production of virus-derived siRNAs and elicited a potent antiviral effect against Enterovirus-A71 (EV-A71) infection in newborn mouse. Our findings demonstrate STUB1 as a novel negative regulator of RNAi by mediating the ubiquitination and degradation of Dicer and AGO proteins, and provide novel insights into the regulatory mechanism of antiviral RNAi in mammals.

2021-11-22 | GSE189203 | GEO

A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity

Project description:CRISPR screens in CD8+ T cells have uncovered novel immunotherapy targets for cancer; however, these screens used activated CD8+ T cells, precluding identification of genes regulating CD8+ T cell priming in the tumor-draining lymph (tdLN). Here we present an 899-gene in vivo CRISPR screen in naive CD8+ T cells, which identifies novel regulators of CD8+ T cell responses in the tdLN and tumor. We find that STUB1, an E3 ubiquitin ligase, significantly regulates CD8+ T cell accumulation in both tissues and Stub1 knockout (KO) CD8+ T cells improve tumor growth control. Mechanistically, STUB1 interacts with the adapter protein, CHIC2, to regulate IL-27Rα, which is required for the increased anti-tumor responses of Stub1 and Chic2 KO CD8+ T cells. Overall, these findings demonstrate that the STUB1-CHIC2 complex is a novel regulator of cytokine receptor expression in CD8+ T cells and provide the rationale for inhibiting this pathway to improve CD8+ T cell-mediated anti-tumor immunity.

2025-08-12 | PXD049402 | Pride

A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity

2025-08-12 | PXD062475 | Pride

STING induces LUBAC synthesis of linear ubiquitin chains to activate NFkB

Project description:STING activation by cyclic dinucleotides in mammals induces Type I Interferon- and NFkB-related gene expression, and the lipidation of LC3B at Golgi membranes. While the mechanisms of the Interferon-related responses are well understood, the mechanism of NFkB activation mediated by STING activation, and how the multi-functional responses downstream of STING signaling are related remain unknown. We report that STING activation induces K63 and linear ubiquitin chain formation, and ubiquitin co-localizes with STING and LC3B at Golgi-derived vesicles. Loss of the LUBAC E3 ubiquitin ligase subunit, HOIP, prevents formation of the linear, but not K63-linked, ubiquitin chains. The ubiquitin and LC3B binding proteins, Optineurin and TNIP1, are co-localized with STING activation-induced, perinuclear LC3B foci via their UBAN domains, however loss of HOIP does not influence this localization, indicating they may bind the K63-linked ubiquitin chains. HOIP-mediated linear ubiquitin chains are well established to mediate NFkB downstream of TNFa and IL1beta receptor stimulation. Loss of HOIP in monocytic THP-1 cells inhibits STING-induced NFkB activation and NFkB-related gene transcription, as well as Interferon-related transcription. Further, the recently reported proton channel activity of STING that blocks LC3B lipidation at Golgi membranes is also important for both K63 and Linear ubiquitin chain formation, and NFkB signaling. Thus, STING induces HOIP and linear ubiquitin chain formation to activate NFkB.

| MSV000092940 | MassIVE

UBIQUITIN LIGASE STUB1 DESTABILIZES IFNγ-RECEPTOR COMPLEX TO SUPPRESS TUMOR IFNγ SIGNALING

Project description:The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about 36 regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identified STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1K285 and JAK1K249. Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This was corroborated by an anticorrelation between STUB1 expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response was increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome.

2022-03-07 | PXD030580 | Pride

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