TTP-mediated regulation of mRNA stability in immune cells contributes to adaptive immunity, immune tolerance and clinical applications

Luo

The Kaohsiung J of Med Scie

et al. 2022

Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay.Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

mentioning

confidence: 99%

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis

Luo

The Kaohsiung J of Med Scie

et al. 2022

“…S3B). Conversely, DCs from males expressed a higher level of negative regulators of DC function, such as Zfp36 ( 30 ), Fos ( 31 ), and Cdkn1a ( 32 ) in LCs (Fig. 3D) and Cd74 , Zfp36 , and Nfkbia in CD11b hi cDC2s (fig.…”

Section: Homeostasis Is Regulated By Male Sex Hormonesmentioning

confidence: 99%

Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

Chi,

Liu,

Gribonika

et al. 2024

Science

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work reveals an androgen-ILC2-DC axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

“…For example, the best known CCCH protein TTP often binds to class II AU-rich elements (AREs; AUUUA) in the 3 -untranslated region (UTR) of target genes including tumour necrosis factor-a (TNF-a) and promotes poly(A)-tail shortening by recruiting the CCR4−CAF1−CNOT1 complex in processing bodies (PBs) or stress granules (SGs) [56][57][58]. It is followed by mRNA degradation catalyzed by the 3 -5 exoribonuclease exosome complex and the 5-cap decapping enzymes DCP1/DCP2 [10]. In this signaling cascade, TTP expression is activated by the released NF-κB in the nucleus derived from IκBα after phosphorylation and degradation in the cytoplasm (Figure 5).…”

Section: Regulatory Mechanisms Of Ccch Proteins In Plants and Animalsmentioning

confidence: 99%

“…The best-studied CCCH protein is human Tristetraprolin (hTTP)/ZFP36, which contains two identical, tandem C-X8-C-X5-C-X3-H motifs separated by 18 amino acids, belonging to typical tandem CCCH Zinc Finger proteins (TZFs) [9]. hTTP/ZFP36 is able to be rapidly activated by serum, insulin and cytokinin and regulates multiple biological processes, such as metabolic disease, inflammatory reaction and embryo development [10]. At the molecular level, hTTP functions through the protein-DNA, protein-RNA and protein-protein interactions.…”

Section: Introductionmentioning

confidence: 99%

Hormone Regulation of CCCH Zinc Finger Proteins in Plants

Wang

Song

et al. 2022

IJMS

CCCH zinc finger proteins contain one to six tandem CCCH motifs composed of three cysteine and one histidine residues and have been widely found in eukaryotes. Plant CCCH proteins control a wide range of developmental and adaptive processes through DNA–protein, RNA–protein and/or protein–protein interactions. The complex networks underlying these processes regulated by plant CCCH proteins are often involved in phytohormones as signal molecules. In this review, we described the evolution of CCCH proteins from green algae to vascular plants and summarized the functions of plant CCCH proteins that are influenced by six major hormones, including abscisic acid, gibberellic acid, brassinosteroid, jasmonate, ethylene and auxin. We further compared the regulatory mechanisms of plant and animal CCCH proteins via hormone signaling. Among them, Arabidopsis AtC3H14, 15 and human hTTP, three typical CCCH proteins, are able to integrate multiple hormones to participate in various biological processes.