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The SRC-family kinase LYN acts as a tumour suppressor gene in an in vivo BRCA1 loss-of-function-associated mammary tumourigenesis model

ABSTRACT: The SRC-family kinase LYN acts as a tumour suppressor gene in an in vivo BRCA1 loss-of-function-associated mammary tumourigenesis model

PROVIDER: PRJNA917599 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22956700_1.fastq.gz	Fastqsanger.gz
	SRR22956700_2.fastq.gz	Fastqsanger.gz
	SRR22956701_1.fastq.gz	Fastqsanger.gz
	SRR22956701_2.fastq.gz	Fastqsanger.gz
	SRR22956702_1.fastq.gz	Fastqsanger.gz

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The SRC-family kinase LYN acts as a tumour suppressor gene in an in vivo BRCA1 loss-of-function-associated mammary tumourigenesis model

Project description:To examine the interaction between LYN kinase and BRCA1 loss-of-function in an in vivo mouse mammary tumour model, we have used conditional knockout Brca1 and Lyn alleles targeted to the mammary epithelium, on a p53 heterozygote background. Comparison of tumour cohorts demonstrated that homozygous conditional Lyn cohorts developed tumours significantly faster than the other genotypes. Transcriptomic analysis to identify and compare tumours with the highest and lowest Lyn levels from across the cohorts showed that ‘Lyn high’ tumours had a significantly slower doubling time and were enriched in inflammatory pathways and canonical NfkB signalling. ‘Lyn low’ tumours had a faster doubling time and were enriched in PI3K, WNT and NOTCH pathways. Therefore, these results suggest that, in this model at least, LYN acts as a tumour suppressor in the context of Brca1 loss.

2023-01-23 | GSE222075 | GEO

Tyrosine Phosphorylation of NLRP3 by Src Family Protein Tyrosine Kinase Lyn Suppresses NLRP3 Inflammasome Activation

Project description:The NLRP3 inflammasome is a multi-protein complex that triggers the activation of the inflammatory protein caspase-1 and the maturation of the cytokine IL-1 in response to microbes and other danger signals in host cells. Here, we sought a deeper understanding of how the NLRP3 inflammasome is regulated. We found that inflammasome activation induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr918, and that this phosphorylation of NLRP3 correlated with a subsequent increase in its ubiquitination, which facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1. Furthermore, mice lacking Lyn were highly susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation of NLRP3 is a prerequisite for its ubiquitination, thus dampening NLRP3 inflammasome activity.

2022-05-19 | PXD028582 | Pride

Src heterodimerically activates Lyn or Fyn to serve as targets for esophageal squamous cell carcinoma (ESCC) diagnosis and treatment

Project description:we combined phosphoproteomics and several cellular and molecular biologic strategies to identify that Src specifically interacted with the members of Src-family kinases (SFKs), such as Fyn or Lyn to form heterodimers, and subsequently phosphorylate the tyrosine sites in SH2 and kinase domains, which critically contributed to the ESCC malignancy.

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Lyn

Project description:Rattus norvegicus Lyn, LYN proto-oncogene, Src family tyrosine kinase [Source:RGD Symbol;Acc:621017], is differentially expressed in 30 experiment(s);

| ENSRNOG00000008180 | ExpressionAtlas

Lyn

Project description:Rattus norvegicus Lyn, LYN proto-oncogene, Src family tyrosine kinase [Source:RGD Symbol;Acc:621017], is expressed in 5 baseline experiment(s);

| ENSRNOG00000008180 | ExpressionAtlas

LYN

Project description:Macaca mulatta LYN, LYN proto-onco, Src family tyrosine kinase [Source:VGNC Symbol;Acc:VGNC:74464], is expressed in 3 baseline experiment(s);

| ENSMMUG00000014149 | ExpressionAtlas

LYN

Project description:Homo sapiens LYN, LYN proto-oncogene, Src family tyrosine kinase [Source:HGNC Symbol;Acc:HGNC:6735], is differentially expressed in 248 experiment(s);

| ENSG00000254087 | ExpressionAtlas

Lyn

Project description:Mus musculus Lyn, LYN proto-oncogene, Src family tyrosine kinase [Source:MGI Symbol;Acc:MGI:96892], is differentially expressed in 141 experiment(s);

| ENSMUSG00000042228 | ExpressionAtlas

LYN

Project description:Oryctolagus cuniculus LYN, LYN proto-oncogene, Src family tyrosine kinase [Source:HGNC Symbol;Acc:HGNC:6735], is expressed in 1 baseline experiment(s);

| ENSOCUG00000003056 | ExpressionAtlas

LYN

Project description:Equus caballus LYN, LYN proto-onco, Src family tyrosine kinase [Source:VGNC Symbol;Acc:VGNC:19852], is expressed in 1 baseline experiment(s);

| ENSECAG00000012862 | ExpressionAtlas

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