A host E3 ubiquitin ligase regulates<i>Salmonella</i>virulence by targeting an SPI-2 effector involved in SIF biogenesis

Meng, Kun; Yang, Jin; Xue, Jian; Jun, LV; Zhu, Ping; Shi, Liu-liu; Li, Shan

doi:10.1101/2022.08.05.502941

Cited by 3 publications

(3 citation statements)

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“…For transient expression in mammalian cells, full open reading frames (ORF) for TRIM1 and HIF1α were amplified using a SW480 cDNA library and inserted into the pCS2-EGFP and pCS2-Flag vectors. pRK5-HA-Ub-WT and the lysine mutants plasmids were maintained in our lab [35]. HRE-luc, pNF-κB-Luc, and pRL-TK reporter plasmids were purchased from Addgene.…”

Section: Materials and Methods Plasmids Antibodies And Reagentsmentioning

confidence: 99%

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

Shi,

Fang,

et al. 2024

Oncogenesis

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Accumulating studies have shown that E3 ligases play crucial roles in regulating cellular biological processes and signaling pathways during carcinogenesis via ubiquitination. Tripartite-motif (TRIM) ubiquitin E3 ligases consist of over 70 members. However, the clinical significance and their contributions to tumorigenesis remain largely unknown. In this study, we analyzed the RNA-sequencing expression of TRIM E3 ligases in colorectal cancer (CRC) and identified 10 differentially expressed genes, among which TRIM1 expression predicted poor prognosis of CRC patients. We demonstrated that TRIM1 expression is positively associated with CRC pathological stages, and higher expression is positively correlated with infiltrating levels of immune cells and immunotherapy biomarkers. TRIM1 expression promotes the proliferation and migration of colorectal cancer cells in vitro and in vivo. Transcriptional analysis showed that TRIM1 is responsible for metabolism promotion and immune suppression. Mechanistically, we found that TRIM1 binds HIF1α and mediates its K63-linked ubiquitination, which is required for HIF1α nuclear translocation and subsequent activation. Ubiquitination occurs at Lys214 in the loop between the two PAS domains of HIF1α, and mutation of Lys214 severely disturbs the function of HIF1α. Besides, HIF1α ubiquitination enhances its binding with proteins involved in cellular trafficking and nucleocytoplasmic transport pathway. Collectively, our results indicate TRIM1’s role in predicting prognosis and reveal how TRIM1 functions to upregulate HIF1α expression and promote tumor cell proliferation.

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Section: Materials and Methods Plasmids Antibodies And Reagentsmentioning

confidence: 99%

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

Shi,

Fang,

et al. 2024

Oncogenesis

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“…SseK3, but not SseK1 or SseK2, interacts with the host E3 ligase TRIM32 yet the significance of this remained unclear as TRIM32 was not identified as a substrate of SseK3, nor is it required for SseK3-mediated inhibition of NF-κB [133,137]. Instead, TRIM32 ubiquitylates SseK3, targeting it for proteasomal degradation and therefore this interaction might represent a host-mediated response to infection [305].…”

Section: Ssek3 and Its Interaction With Trim32mentioning

confidence: 99%

Speaking the host language: how Salmonella effector proteins manipulate the host

Pillay,

Hettiarachchi,

Gan

et al. 2023

Microbiology

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Salmonella injects over 40 virulence factors, termed effectors, into host cells to subvert diverse host cellular processes. Of these 40 Salmonella effectors, at least 25 have been described as mediating eukaryotic-like, biochemical post-translational modifications (PTMs) of host proteins, altering the outcome of infection. The downstream changes mediated by an effector’s enzymatic activity range from highly specific to multifunctional, and altogether their combined action impacts the function of an impressive array of host cellular processes, including signal transduction, membrane trafficking, and both innate and adaptive immune responses. Salmonella and related Gram-negative pathogens have been a rich resource for the discovery of unique enzymatic activities, expanding our understanding of host signalling networks, bacterial pathogenesis as well as basic biochemistry. In this review, we provide an up-to-date assessment of host manipulation mediated by the Salmonella type III secretion system injectosome, exploring the cellular effects of diverse effector activities with a particular focus on PTMs and the implications for infection outcomes. We also highlight activities and functions of numerous effectors that remain poorly characterized.

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“…For transient expression in mammalian cells, full open reading frames (ORF) for TRIM1 and HIF1α were ampli ed using a SW480 cDNA library and inserted into the pCS2-EGFP and pCS2-Flag vectors. pRK5-HA-Ub-WT and the lysine mutants plasmids were maintained in our lab (27) . HRE-luc, pNF-κB-Luc, and pRL-TK reporter plasmids were purchased from Addgene.…”

Section: Plasmids Antibodies and Reagentsmentioning

confidence: 99%

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

Meng,

Shi,

Fang

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Accumulating studies have shown that E3 ligases play crucial roles in regulating cellular biological processes and signaling pathways during carcinogenesis via ubiquitination. Tripartite-motif (TRIM) ubiquitin E3 ligases consist of over 70 members. However, the clinical significance and their contributions to tumorigenesis remain largely unknown. In this study, we analyzed the RNA-sequencing expression of TRIM E3 ligases in colorectal cancer (CRC) and identified 10 differentially expressed genes, among which TRIM1 expression predicted poor prognosis of CRC patients. We demonstrated that TRIM1 expression is positively associated with CRC pathological stages, and higher expression is positively correlated with infiltrating levels of immune cells and immunotherapy biomarkers. TRIM1 expression promotes the proliferation and migration of colorectal cancer cells. Transcriptional analysis showed that TRIM1 is responsible for metabolism promotion and immune suppression. Mechanistically, we found that TRIM1 binds HIF1α and mediates its K63-linked ubiquitination, which is required for HIF-1α nuclear translocation and subsequent activation. Our results indicate TRIM1’s role in predicting prognosis and immunotherapy efficacy and reveal how TRIM1 functions to upregulate HIF-1α expression and promote tumor cell proliferation.

show abstract

A host E3 ubiquitin ligase regulatesSalmonellavirulence by targeting an SPI-2 effector involved in SIF biogenesis

Cited by 3 publications

References 50 publications

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

Speaking the host language: how Salmonella effector proteins manipulate the host

An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α

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