更新于：2024-11-01

TASL

更新于：2024-11-01

基本信息

别名

CXorf21、FLJ11577、TASL

+ [2]

简介

Innate immune adapter that mediates the recruitment and activation of IRF5 downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:32433612). Following recruitment to endolysosome by SLC15A4 downstream of TLR7, TLR8 and TLR9, specifically recruits IRF5 transcription factor via its pLxIS motif, leading to IRF5 activation and subsequent expression of type I interferons (PubMed:32433612). Plays a role in the regulation of endolysosomal pH in immune cells such as B-cells, dendritic cells and monocytes (PubMed:31001245).

关联

项与 TASL 相关的药物

Feeblin

靶点

TASL

作用机制

TASL抑制剂

在研机构

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

原研机构

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

在研适应症

系统性红斑狼疮

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TASL 相关的临床结果

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100 项与 TASL 相关的转化医学

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0 项与 TASL 相关的专利（医药）

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项与 TASL 相关的文献（医药）

2024-08-01·Current Opinion in Cell Biology

New advances in innate immune endosomal trafficking

Review

作者: Li, Xichun ; Stow, Jennifer L ; Stocks, Claudia J

The exocytic and endocytic intracellular trafficking pathways in innate immune cells are known for mediating the secretion of key inflammatory mediators or the internalization of growth factors, nutrients, antigens, cell debris, pathogens and even therapeutics, respectively. Inside cells, these pathways are intertwined as an elaborate network that supports the regulation of immune functions. Endosomal membranes host dynamic platforms for molecular complexes that control signaling and inflammatory responses. High content screens, coupled with elegant microscopy across the scale of resolving molecular complexes to tracking live cellular organelles, have been employed to generate the studies highlighted here. With a focus on deactivation of STING, scaffolding by SLC15A4/TASL complexes and macropinosome shrinkage via the chloride channel protein TMEM206, new studies are identifying molecules, molecular interactions and mechanisms for immune regulation throughout endosomal pathways.

2024-06-01·American Journal of Medical Genetics Part A

X‐linked congenital adrenal hypoplasia: Report of long clinical follow‐up and description of a new complex variant in the NR0B1 gene

Article

作者: Guaragna, Mara Sanches ; Guerra-Junior, Gil ; da Silva Lopes, Vera Lúcia Gil ; Esquiaveto-Aun, Adriana Mangue ; Mazolla, Taís Nitsh ; Dos Santos Cruz Piveta, Cristiane ; de Mello, Maricilda Palandi ; Francese-Santos, Ana Paula ; de Lemos-Marini, Sofia Helena Valente

AbstractAdrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype–phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow‐up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion–insertion–inversion–deletion complex rearrangement sorted in the 5′‐3′ direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5′ region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3′UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end‐joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an “information scar,” represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.

2024-04-01·Plant Biotechnology Journal

MicroRNA482/2118 is lineage‐specifically involved in gibberellin signalling via the regulation of GID1 expression by targeting noncoding PHAS genes and subsequently instigated phasiRNAs

Article

作者: Li, Guanliang ; Liu, Yuanlong ; Zhang, Yanqing ; Ma, Xingshuai ; Chen, Chengjie ; Hao, Yanwei ; Xu, Jing ; Xia, Rui ; Hu, Huimin ; Li, Jianguo ; Zhao, Minglei ; Zeng, Zaohai

SummaryMicroRNA482/2118 (miR482/2118) is a 22‐nt miRNA superfamily, with conserved functions in disease resistance and plant development. It usually instigates the production of phased small interfering RNAs (phasiRNAs) from its targets to expand or reinforce its silencing effect. Using a new high‐quality reference genome sequence and comprehensive small RNA profiling, we characterized a newly evolved regulatory pathway of miR482/2118 in litchi. In this pathway, miR482/2118 cleaved a novel noncoding trans‐acting gene (LcTASL1) and triggered phasiRNAs to regulate the expression of gibberellin (GA) receptor gene GIBBERELLIN INSENSITIVE DWARF1 (GID1) in trans; another trans‐acting gene LcTASL2, targeted by LcTASL1‐derived phasiRNAs, produced phasiRNAs as well to target LcGID1 to reinforce the silencing effect of LcTASL1. We found this miR482/2118‐TASL‐GID1 pathway was likely involved in fruit development, especially the seed development in litchi. In vivo construction of the miR482a‐TASL‐GID1 pathway in Arabidopsis could lead to defects in flower and silique development, analogous to the phenotype of gid1 mutants. Finally, we found that a GA‐responsive transcription factor, LcGAMYB33, could regulate LcMIR482/2118 as a feedback mechanism of the sRNA‐silencing pathway. Our results deciphered a lineage‐specifically evolved regulatory module of miR482/2118, demonstrating the high dynamics of miR482/2118 function in plants.