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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response

ABSTRACT: Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response

PROVIDER: PRJNA1061572 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27442453.fastq.gz	Fastqsanger.gz
	SRR27442454.fastq.gz	Fastqsanger.gz
	SRR27442455.fastq.gz	Fastqsanger.gz
	SRR27442456.fastq.gz	Fastqsanger.gz
	SRR27442457_1.fastq.gz	Fastqsanger.gz

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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [CRISPR]

Project description:The ubiquitination and proteasome-mediated degradation of Hypoxia Inducible Factors (HIFs) is central to metazoan oxygen-sensing, but the involvement of deubiquitinating enzymes (DUBs) in HIF signalling is less clear. Here, using a bespoke DUBs sgRNA library we conduct CRISPR/Cas9 mutagenesis screens to determine how DUBs are involved in HIF signalling. Alongside defining DUBs involved in HIF activation or suppression, we identify USP43 as a DUB required for efficient activation of a HIF response. USP43 is hypoxia regulated and selectively associates with the HIF-1 isoform, and while USP43 does not alter HIF-1 stability, it facilitates HIF-1 nuclear accumulation and binding to its target genes. Mechanistically, USP43 associates with 14-3-3 proteins in a hypoxia-dependent manner to increase the nuclear pool of HIF-1, independently of DUB activity. Together, our results unveil the DUB landscape in HIF signalling, and highlight the multifunctionality of DUBs, illustrating that they can provide important signalling roles outside of their catalytic activity.

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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [CRISPR]

Project description:Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [CRISPR]

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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [RNA-seq]

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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [RNA-seq]

Project description:Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [RNA-seq]

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Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response

Project description:The ubiquitination and proteasome-mediated degradation of hypoxia-inducible factors (HIFs) is central to metazoan oxygen-sensing, but the involvement of deubiquitinating enzymes (DUBs) in HIF signalling is less clear. Here, we conduct CRISPR/Cas9 mutagenesis screens using a bespoke DUBs sgRNA library to determine how DUBs are involved in HIF signalling. Alongside defining DUBs involved in HIF activation or suppression, we identify USP43 as a DUB required for efficient activation of a HIF response. USP43 is hypoxia-regulated and selectively associates with the HIF-1alpha isoform. While USP43 does not alter HIF-1alpha stability, it facilitates HIF-1 nuclear accumulation and binding to its target genes. Mechanistically, USP43 associates with 14-3-3 proteins in a hypoxia- and phosphorylation-dependent manner to increase the nuclear pool of HIF-1. Together, our results highlight the multifunctionality of DUBs, illustrating that they can provide important signalling functions alongside their catalytic roles.

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Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response

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

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Transcriptional studies on the deubiquitinating enzyme Ubp10

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