Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Shigella kinase effector OspG hijacks host ubiquitin signaling to escape septin-cage entrapment

ABSTRACT: We show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiaoyun Liu

PROVIDER: PXD048447 | iProX | Wed Jan 10 00:00:00 GMT 2024

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Xian Wei W Fu Jiaqi J Zhang Qinxin Q Li Chuang C Zhao Yan-Bo YB Tang Zhiheng Z Yuan Yi Y Wang Ying Y Zhou Yan Y Brzoic Peter S PS Zheng Ning N Ouyang Songying S Luo Zhao-Qing ZQ Liu Xiaoyun X

Nature communications 20240508 1

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CA ...[more]

PMID: 38719850

Similar Datasets

E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification

Project description:Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificity established? Here we report that, like UBE2M (also known as UBC12), the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro and in vivo. Biochemical and structural analyses indicate how plasticity of hydrophobic E1-E2 interactions and E1 conformational flexibility allow one E1 to charge multiple E2s. The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities. Together, these studies reveal the molecular basis for and functional importance of hierarchical expansion of the NEDD8 conjugation system in establishing selective CRL activation. Mol Cell 33:483-495, 2009. Keywords: Comparison of gene expression profiles Ube2m and Ube2f are E2 enzymes that direct protein modification by NEDD8. Here we explore the specific functions of Ube2f and Ube2m by comparing gene expression profiles following knockdown of their function in NIH 3T3 cells. We used microarrays to detail the global programme of gene expression changes following knockdown of Ube2m and Ube2f in NIH 3T3 cells. NIH 3T3 cells were transduced with retroviral constructs containing shRNA directed against Ube2m or Ube2f. Three replicates of each condition were analyzed.

2009-03-23 | E-GEOD-14088 | biostudies-arrayexpress

E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification

2009-03-24 | GSE14088 | GEO

The p53-dependent role of JAB1 in OS pathogenesis

Project description:JAB1 is a regulator of ubiquitin mediated protein degradation upstream of the 26S proteasome. JAB1 regulates the ubiquitin proteasome system through controlling the activity of the largest family of E3 ubiquitin ligases, the Cullin-RING Ligases. JAB1 is also a transcriptional co-factor contolling the expression of numerous genes and regulates musculoskeletal development in vivo. It is reported that JAB1 is overexpressed in many cancers, making it a potential oncogene. Thus, JAB1 has a highly spatiotemporal specific role in development and cancer pathogenesis. This study aims to determine the JAB1-mediated transcriptome that exists in osteosarcoma cells.

2020-06-10 | GSE117773 | GEO

Transcriptional Regulation by Cullin Ubiquitin Ligases

Project description:Transcriptional Regulation by Cullin Ubiquitin Ligases

| PRJNA614537 | ENA

Dual BACH1 regulation by complementary SCF-type E3 ligases

Project description:BACH1, FBXO22, FBXL17, oxidative stress response, E3, Cullin-RING ligases, F-box, cysteine modification, S-nitrosylation, heme

2024-12-03 | PXD051074 | Pride

Functional characterisation of Cullin-Ring-Ligases in Plasmodium falciparum

Project description:Ubiquitination is the key post-translational modification in eukaryotic cells that governs protein degradation, localisation, and activity. This process results in the tagging of ubiquitin to protein substrates by a concerted enzyme cascade of E1, E2 and E3 enzymes. The largest superfamily of these proteins includes the Cullin-Ring-Ligase (CRL) complexes of E3 ligases. Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, encodes the critical proteins required for ubiquitination, but we do not yet understand the function of this pathway. Here the P. falciparum CRL E3 ligases were characterised to reveal an essential but minimal repertoire controlled by two Cullin scaffolds. A PfCullin1-linked CRL complex was identified as being required for parasite inner-membrane biogenesis and DNA replication. This complex recruits only one substrate receptor, compared to the ~70 receptors used interchangeably by human cells. A second CRL complex functioning through a PfCullin4 scaffold was identified that utilised a previously unidentified adaptor protein and receptors to support DNA replication. These results show that the P. falciparum E3 ubiquitin ligases play an essential role in the biology of this important infectious agent.

2025-07-11 | PXD063957 | Pride

The Hace1 E3 Ligase Modulates the Activity of Multiple Tumor Suppressive CRL E3 Ligases by binding to CAND1

Project description:The Hace1 E3 ligase is a tumor suppressor in stressed cells. Through unknown mechanisms, Hace1 indirectly targets the cyclin D1 proto-oncogene for proteasomal degradation during nutrient depletion. We now show that Hace1 targets HIF1alpha for VHL-dependent degradation during hypoxia. To better understand these diverse actions we performed mass spectrometry to identify Hace1-interacting proteins. We show that Hace1 interacts with cullin-associated NEDD8-dissociated protein 1 (CAND1) under nutrient depletion and hypoxia. CAND1 binds cullins and prevents their entry into cullin ring E3 ligase (CRL) complexes, thus blocking CRL activity. Hace1 binding releases CUL1/2 from CAND1, facilitating assembly of CRL complexes to degrade cyclin D1 and HIF1alpha, respectively. These findings suggest a broad role for Hace1 in regulating tumor suppressive CRL E3 ligases. In this study, we used gene expression profiling to characterize how Hace1 overexpression affect the transcriptional response to hypoxic stress Using Affymetrix exon-level microarrays, we compared the expression profile of HEK293 cells overexpressing either Hace1 or MSCV vector alone, under hypoxia or normoxia

2011-07-01 | E-GEOD-25452 | biostudies-arrayexpress

Changes in Cereblon substrates landscape upon molecular glue treatment

Project description:The specificity of the ubiquitination process is mediated by the E3 ligases. Discriminating specific substrates of E3s from interacting proteins is one of the major challenges in the field. We previously developed BioE3, a biotin-based approach that uses BirA-E3 fusions together with ubiquitin fused to a low-affinity AviTag to obtain a site-specific and proximity-dependent biotinylation of the target proteins. We proved the suitability of BioE3 to identify targets of RING and HECT-type E3 ligases. Here we demonstrate that the system is suitable for the multi-protein complex Cullin-RING E3s, choosing as proof of principle the substrate receptor CRBN. We identified both CRBN endogenous substrates and new neosubstrates upon pomalidomide treatment, including CSDE1 which contains a new motif involved in the binding to CRBN in presence of pomalidomide. Importantly, we observed a major rearrangement of the endogenous ubiquitination landscape upon this molecular glue treatment. The ability of our system to detect changes in the specificity of the E3s in response to drugs may be of interest in the development of targeted protein degradation strategies.

2025-05-07 | PXD055877 | Pride

Differential expression of proteins in hematopoietic stem/progenitor cells lacking the Cullin-5 protein

Project description:Cullin proteins are scaffolds that coordinate assembly of cullin-RING E3 ubiquitin (Ub) ligases (CRL), complexes that control post-translational ubiquitin modification and degradation of cellular proteins. Cullin-5 (Cul5) coordinates assembly of CRL complexes containing the RING E3 ligase Rbx1/2, the adapter proteins Elongins B and C, and a Suppressor of Cytokine Signalling (SOCS) box-containing substrate recognition protein. To explore potential roles for Cul5, we generated mice lacking Cul5 in the in hematopoietic system. Analyses included biological and molecular studies including proteomic analysis of differential expression of proteins in primary purified hematopoietic stem/progenitor (LSK) cells lacking Cul5.

2025-01-26 | PXD051430 | Pride

Identification of the NEDDylated proteome by Nedd8-specific K-GG mass spectrometry uncovers modulation of Actin dynamics by neddylated Cofilin

Project description:Neddylation is the post-translational protein modification that is most closely related to ubiquitination. The Ubiquitin-like protein NEDD8 is mostly studied for its role in activating the Cullin-RING E3 Ubiquitin ligases, however little is known about other NEDD8 targets. We developed serial NEDD8-Ubiquitin Substrate Profiling (sNUSP), a method that employs Nedd8-R74K knock-in cells allowing discrimination of endogenous NEDD8- and Ubiquitin-modification sites by mass spectrometry after Lys-C digestion and K-GG- peptide enrichment. Using sNUSP, we identified 607 neddylation sites dynamically regulated by the neddylation inhibitor MLN4924 and the de-neddylating enzyme NEDP1/SENP8. Among the candidates, we characterized lysine 112 (K112) of the Actin regulator Cofilin as a novel neddylation event. Global inhibition of neddylation in developing neurons leads to cytoskeletal defects, altered Actin dynamics and neurite growth impairments and site-specific neddylation of Cofilin at K112 regulates neurite outgrowth. These data show that Cofilin neddylation contributes to the regulation of neuronal Actin dynamics.

2019-12-12 | MSV000084683 | MassIVE

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