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Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [Bulk RNA-seq]

ABSTRACT: Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [Bulk RNA-seq]

PROVIDER: PRJNA891293 | ENA |

REPOSITORIES: ENA

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Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma

Project description:Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma

| PRJNA891671 | ENA

Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [scRNA-seq]

Project description:Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [scRNA-seq]

| PRJNA891679 | ENA

Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [scRNA-seq]

Project description:Tumor microenvironment components, including T and myeloid cells, play important roles in lung adenocarcinoma (LADC) progression and response to therapy. Here, we identify a role for Siah1a/2 ubiquitin ligases in controlling alveolar macrophage (AM) differentiation and urethane-induced LADC. Genetic ablation of Siah1a/2 in AMs enriched their immature state, coinciding with increased pro-tumorigenic and inflammatory gene signatures and abundance of Siah1a/2 substrates NRF2 and B-catenin. Urethane administration to mice enriched the population of monocytic and immature-like AMs, which were more prevalent in the lungs of mice carrying Siah1a/2-ablated macrophages. While resembling transitional profibrotic macrophages often seen in lung fibrosis, enrichment of immature AMs coincided with the development of more frequent and larger lung tumors in urethane-treated mice harboring Siah1a/2 ablated macrophages compared with controls. Gene expression signature of Siah1a/2 ablated immature-like AMs is associated with increased infiltration of CD14+ immune cells and worse survival of LADC patients. Our findings identify Siah1a/2 as gatekeepers of cancer development by controlling AM differentiation and profibrotic phenotypes contributing to carcinogen-induced lung cancer.

2023-05-15 | GSE215992 | GEO

Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [Bulk RNA-seq]

2023-05-15 | GSE215920 | GEO

Transcriptional Regulation by Cullin Ubiquitin Ligases

Project description:Transcriptional Regulation by Cullin Ubiquitin Ligases

| PRJNA614537 | ENA

Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-15 | GSE215993 | GEO

Structural basis for substrate recognition and chemical inhibition of oncogenic MAGE ubiquitin ligases

Project description:Testis-restricted melanoma antigen (MAGE) proteins are frequently hijacked in cancer and play a critical role in tumorigenesis. MAGEs assemble with E3 ubiquitin ligases and function as substrate adaptors that direct the ubiquitination of novel targets, including key tumor suppressors. However, how MAGEs recognize their targets is unknown and has impeded development of MAGE-directed therapeutics. Here, we report the structural basis for substrate recognition by MAGE ubiquitin ligases. Biochemical analysis of the degron motif recognized by MAGE-A11 and the crystal structure of MAGE-A11 bound to the PCF11 substrate uncovered a conserved substrate binding cleft (SBC) in MAGEs. Mutation of the SBC disrupted substrate recognition by MAGEs and blocked MAGE-A11 oncogenic activity. A chemical screen for inhibitors of MAGE-A11:substrate interaction identified 4-aminoquniolines as potent inhibitors of MAGE-A11 that show selective cytotoxicity. These findings provide important insights into the large family of MAGE ubiquitin ligases and identify approaches for development of cancer-specific therapeutics.

2020-08-15 | GSE148458 | GEO

To identify potential ubiquitin ligases that regulate BIK1 homeostasis

Project description:To identify potential ubiquitin ligases that regulate BIK1 homeostasis

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To identify potential ubiquitin ligases that regulate BIK1 homeostasis

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2023-06-14 | GSE227628 | GEO

SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

Project description:SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

| PRJNA742677 | ENA