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SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

ABSTRACT: SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

PROVIDER: PRJNA742677 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15000280.fastq.gz	Fastqsanger.gz
	SRR15000281.fastq.gz	Fastqsanger.gz
	SRR15000282.fastq.gz	Fastqsanger.gz
	SRR15000283.fastq.gz	Fastqsanger.gz
	SRR15000284.fastq.gz	Fastqsanger.gz

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SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression

Project description:The functionally redundant ubiquitin E3 ligases SIAH1 and SIAH2 have been implicated in the regulation of several processes, but their role in inflammatory signaling and gene expression remains unclear. Here we have downregulated the expression of both SIAH proteins with specific siRNAs and investigated the functional consequences for IL-1α-induced gene expression and the signaling pathways activating NF-κB and AP1. The knockdown of SIAH1/2 had no significant impact on IL-1α-induced activation of NF-κB and MAPK signaling pathways, but modulated the expression of approximately one third of IL-1α-regulated genes. Most of the proteins encoded by SIAH1/2-regulated genes form a regulatory network of proinflammatory factors. Thus SIAH1/2 proteins function as variable rheostats that control the amplitude of inflammatory gene expression.

2022-02-01 | GSE179190 | GEO

Repurposing E3 ubiquitin ligases as cell surface protein degraders using Proteolysis Targeting Antibodies

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Paeonia lactiflora suppressed cancer-cachexia by downregulating muscular NF-κB signaling and muscle-specific E3 ubiquitin ligases in cancer-bearing mice.

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Repurposing E3 ubiquitin ligases as cell surface protein degraders using Proteolysis Targeting Antibodies

Project description:Repurposing E3 ubiquitin ligases as cell surface protein degraders using Proteolysis Targeting Antibodies

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Transcriptional Regulation by Cullin Ubiquitin Ligases

Project description:Transcriptional Regulation by Cullin Ubiquitin Ligases

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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.

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SIAH ubiquitin E3 ligases as modulators of inflammatory gene expression.

Project description:The functionally redundant ubiquitin E3 ligases SIAH1 and SIAH2 have been implicated in the regulation of metabolism and the hypoxic response, while their role in other signal-mediated processes such inflammatory gene expression remains to be defined. Here we have downregulated the expression of both SIAH proteins with specific siRNAs and investigated the functional consequences for IL-1α-induced gene expression. The knockdown of SIAH1/2 modulated the expression of approximately one third of IL-1α-regulated genes. These effects were not due to changes in the NF-κB and MAPK signaling pathways and rather employed further processes including those mediated by the coactivator p300. Most of the proteins encoded by SIAH1/2-regulated genes form a regulatory network of proinflammatory factors. Thus SIAH1/2 proteins function as variable rheostats that control the amplitude rather than the principal activation of the inflammatory gene response.

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

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