Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation

Yu, Guiping; Chen, Yiqi; Hu, Yu-Wen; Zhou, Yan; Ding, Xiaoling; Zhou, Xiaorong

doi:10.3389/fcell.2022.1010639

Cited by 9 publications

(5 citation statements)

References 233 publications

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“…On the one side, it is flanked by ddb2 (Damage‐specific DNA Binding Protein 2), a gene that is involved in DNA repair and maintenance of genomic stability (Rapić‐Otrin et al, 2003). On the other side, it is located near LOC106584812, a gene with a product similar to transducin‐like enhancer protein 3 (TLE3), a member of the TLE family of proteins involved in several crucial aspects of development, including segmentation, neural development and Wnt signalling (Yu et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

From viral load to survival: Unveiling new genetic links for resistance against PMCV in Atlantic Salmon (Salmo salar)

Mogahadam,

Røsæg

2023

Journal of Fish Diseases

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The infectious agent piscine myocarditis virus (PMCV) causes cardiomyopathy syndrome (CMS) and is responsible for substantial mortality and economic losses in the Atlantic salmon (Salmo salar) farming industry. Previous research has demonstrated that breeding for resistance against PMCV is an effective approach to mitigate the disease's impact. In this study, a new quantitative trait locus (QTL) is described on chromosome 23, together with previously described QTLs on chromosomes 12 and 27. The findings are based on two genome‐wide association studies conducted on two different year‐classes of Atlantic salmon of the Rauma strain. In this study, we utilized data from an experimental challenge trial with the viral load as the phenotype and a field outbreak of CMS with survival data as the phenotype. The estimated SNP‐based heritability was 0.55 and 0.44 in the two studies, respectively. In the infection trial, the top associated SNP on chromosome 23 accounted for approximately 46% of the genetic and 25.53% of the phenotypic variations in the viral load. In the field outbreak, we identified a QTL on the same genomic region of chromosome 23. The most significantly associated marker on this chromosome explained 13.57% and 5.97% of the genetic and phenotypic variations. The QTL on chromosome 23 is in proximity to delta‐5 fatty acyl desaturase and fatty acid desaturase 2 genes, both of which play a role in the production of polyunsaturated fatty acids. This proximity is particularly interesting as it offers valuable insights into enhancing our understanding of resistance against PMCV.

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Section: Resultsmentioning

confidence: 99%

From viral load to survival: Unveiling new genetic links for resistance against PMCV in Atlantic Salmon (Salmo salar)

Mogahadam,

Røsæg

2023

Journal of Fish Diseases

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“…LSAMP is a tumor suppressor gene in osteosarcoma 53 , and 3q13.31 homozygous deletions have been implicated in tumorigenesis 54 . TLE3 is a transcriptional corepressor involved in tumorigenesis and immune function 55 . The transcription factor TULP3 has been implicated in pancreatic ductal adenocarcinoma and colorectal cancer 56 .…”

Section: Discussionmentioning

confidence: 99%

Multi-ancestry meta-analyses of lung cancer in the Million Veteran Program reveal novel risk loci and elucidate smoking-independent genetic risk

Gorman,

Ji,

Francis

et al. 2024

Preprint

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Lung cancer remains the leading cause of cancer mortality, despite declines in smoking rates. Previous lung cancer genome-wide association studies (GWAS) have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. We performed multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program (MVP) cohort and a previous study of European-ancestry individuals, comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We further performed conditional meta-analyses on cigarettes per day and identified two novel, replicated loci, including the 19p13.11 pleiotropic cancer locus in LUSC. Overall, we report twelve novel risk loci for overall lung cancer, lung adenocarcinoma (LUAD), and squamous cell lung carcinoma (LUSC), nine of which were externally replicated. Finally, we performed phenome-wide association studies (PheWAS) on polygenic risk scores (PRS) for lung cancer, with and without conditioning on smoking. The unconditioned lung cancer PRS was associated with smoking status in controls, illustrating reduced predictive utility in non-smokers. Additionally, our PRS demonstrates smoking-independent pleiotropy of lung cancer risk across neoplasms and metabolic traits.

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“…All these results point to a mode of action were Tle4 and Hes1 do not directly interact with Sox10 or directly impede its binding to target gene regulatory regions. Tle proteins were shown to shut down gene expression of their target genes using different modes of action (for detailed information, see [46]). Depending on their binding partners they may be recruited to their target genes by DNA-binding transcriptional repressors, such as Hes proteins, and together with them, recruit HDACs or other silencing complexes generating a non-accessible chromatin landscape for activating transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop

Aberle,

Walter,

Piefke

et al. 2024

IJMS

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The HMG-domain containing transcription factor Sox10 plays a crucial role in regulating Schwann cell survival and differentiation and is expressed throughout the entire Schwann cell lineage. While its importance in peripheral myelination is well established, little is known about its role in the early stages of Schwann cell development. In a search for direct target genes of Sox10 in Schwann cell precursors, the transcriptional co-repressor Tle4 was identified. At least two regions upstream of the Tle4 gene appear involved in mediating the Sox10-dependent activation. Once induced, Tle4 works in tandem with the bHLH transcriptional repressor Hes1 and exerts a dual inhibitory effect on Sox10 by preventing the Sox10 protein from transcriptionally activating maturation genes and by suppressing Sox10 expression through known enhancers of the gene. This mechanism establishes a regulatory barrier that prevents premature activation of factors involved in differentiation and myelin formation by Sox10 in immature Schwann cells. The identification of Tle4 as a critical downstream target of Sox10 sheds light on the gene regulatory network in the early phases of Schwann cell development. It unravels an elaborate regulatory circuitry that fine-tunes the timing and extent of Schwann cell differentiation and myelin gene expression.

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Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation

Cited by 9 publications

References 233 publications

From viral load to survival: Unveiling new genetic links for resistance against PMCV in Atlantic Salmon (Salmo salar)

From viral load to survival: Unveiling new genetic links for resistance against PMCV in Atlantic Salmon (Salmo salar)

Multi-ancestry meta-analyses of lung cancer in the Million Veteran Program reveal novel risk loci and elucidate smoking-independent genetic risk

Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop

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