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Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [ChIP-seq]

ABSTRACT: Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [ChIP-seq]

PROVIDER: PRJNA865741 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20796326.fastq.gz	Fastqsanger.gz
	SRR20796327.fastq.gz	Fastqsanger.gz
	SRR20796328.fastq.gz	Fastqsanger.gz
	SRR20796329.fastq.gz	Fastqsanger.gz
	SRR20796330.fastq.gz	Fastqsanger.gz

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Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes

Project description:Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes

| PRJNA865752 | ENA

Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [RNA-seq]

Project description:Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [RNA-seq]

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Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [RNA-seq]

Project description:The involvement of G-Protein-Coupled Receptors’ (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, capable of signaling intranuclearly to induce nuclear-ERK and AKT phosphorylation concomitant with higher cancer cell proliferation and survival. We determine its nuclear interactome, proving its involvement in protein-translation and DNA-damage repair. Nuclear HCAR1 (N-HCAR1) directly interacts with chromatin/DNA promoting expression of genes involved in cellular migration. Notably, we show N-HCAR1 particularly regulates a broader transcriptomic signature than its PM counterpart, emphasizing on the facts that functional output of N-HCAR1 is larger than PM localized HCAR1. Our study presents several unprecedented processes by which a GPCR through location-biased activity regulate various cellular functions and how cancer cells exploit these.

2023-11-15 | GSE210469 | GEO

Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes [ChIP-seq]

2023-11-15 | GSE210455 | GEO

Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes

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

2023-11-15 | GSE210470 | GEO

Bias musicus

Project description:Bias musicus

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Dye Bias Array Set

Project description:Spot intensity serves as a proxy for gene expression in dual-label microarray experiments. Dye bias is defined as an intensity difference between samples labeled with different dyes attributable to the dyes instead of the gene expression in the samples. Dye bias that is not removed by array normalization can introduce bias into comparisons between samples of interest. But if the bias is consistent across the samples for the same gene, it can be corrected by proper experimental design and analysis. If the dye bias is not consistent across samples for the same gene, but is different for different samples, then removing the bias becomes more problematic, perhaps indicating a technical limitation to the ability of fluorescent signals to accurately represent gene expression. Thus, it is important to characterize dye bias to determine: (1) whether it will be removed for all genes by array normalization, (2) whether it will not be removed by normalization but can be removed by proper experimental design and analysis and (3) whether dye bias correction is more problematic than either of these and is not easily removable. Keywords: dye swap design

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Investigating PCR bias in TnSeq

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mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations

Project description:Numerous proteins are targeted to two or multiple subcellular destinations where they exert distinct functional consequences. The balance between such differential targeting is thought to be determined post-translationally, relying on protein sorting mechanisms. Here, we show that protein targeting can additionally be determined by mRNA location and translation rate. Our model, the NET1 protein, distributes between the nucleus and cytosol and functions in cell motility. N-terminal NLSs and an internal PH domain competitively determine NET1 distribution. Peripheral localization of the NET1 mRNA and fast translation lead to higher cytosolic retention through the PH domain. By contrast, perinuclear mRNA location and/or slower translation rate favor nuclear targeting through importin β1. NET1 mRNA location is modulated by physiological stimuli and profoundly impacts NET1 function in cell motility. Indeed, perinuclear NET1 mRNA localization causes reduced RhoA activity, impedes focal adhesion maturation and results in slower cell migration to an extent similar as that observed upon knockdown of NET1 expression. Overall, these results reveal that the location of protein synthesis and the rate of translation elongation act in coordination to influence the ability of competing domains within a polypeptide to determine protein distribution and function.

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Oxoeicosanoid signaling promotes early antimicrobial defense in zebrafish (Danio rerio)

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