Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2

Imamura, Masataka; Higashi, Kyohei; Yamaguchi, Katsutoshi; Asakura, Kiryu; Furihata, Tomomi; Terui, Yusuke; Satake, Toshihiko; Maegawa, Jiro; Yasumura, Keisuke; Ibuki, Ai; Akase, Tomoko; Nishimura, Kazuhiro; Kashiwagi, Keiko; Linhardt, Robert J.; Igarashi, Kazuei; Toida, Toshihiko

doi:10.1038/srep33549

Cited by 25 publications

(21 citation statements)

References 62 publications

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“…Microscale isolation of glycosaminoglycans (GAGs) was performed using an anion exchange spin column with minor modifications (Imamura et al 2016). Brain tissues were lyophilized until they were dry.…”

Section: Disaccharide Analysismentioning

confidence: 99%

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Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche

Yamada

Kerever

Yoshimura

et al. 2017

Journal of Neurochemistry

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Adult neurogenesis in the subventricular zone of the lateral ventricle decreases with age. In the subventricular zone, the specialized extracellular matrix structures, known as fractones, contact neural stem cells and regulate neurogenesis. Fractones are composed of extracellular matrix components, such as heparan sulfate proteoglycans. We previously found that fractones capture and store fibroblast growth factor 2 (FGF-2) via heparan sulfate binding, and may deliver FGF-2 to neural stem cells in a timely manner. The heparan sulfate (HS) chains in the fractones of the aged subventricular zone are modified based on immunohistochemistry. However, how aging affects fractone composition and subsequent FGF-2 signaling and neurogenesis remains unknown. The formation of the FGF-fibroblast growth factor receptor-HS complex is necessary to activate FGF-2 signaling and induce the phosphorylation of extracellular signal-regulated kinase (Erk1/2). In this study, we observed a reduction in HS 6-O-sulfation, which is critical for FGF-2 signal transduction, and failure of the FGF-2-induced phosphorylation of Erk1/2 in the aged subventricular zone. In addition, we observed increased HS 6-O-endo-sulfatase, an enzyme that may be responsible for the HS modifications in aged fractones. In conclusion, the data revealed that heparan sulfate 6-O-sulfation is reduced and FGF-2-dependent Erk1/2 signaling is impaired in the aged subventricular zone. HS modifications in fractones might play a role in the reduced neurogenic activity in aging brains.

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Section: Disaccharide Analysismentioning

confidence: 99%

“…Unsaturated disaccharide analysis was conducted with reverse phase ion-pair chromatography using sensitive and specific postcolumn detection (Imamura et al 2016).…”

Section: Disaccharide Analysismentioning

confidence: 99%

Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche

Yamada

Kerever

Yoshimura

et al. 2017

Journal of Neurochemistry

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“…As a result, it was found that syntheses of EXT1 and EXT2 were enhanced by polyamines at the level of translation (Fig. 3A) (10).…”

Section: Nm)mentioning

confidence: 87%

“…The distribution and number of protein-binding sites containing IdoA and di-sulfated disaccharides in the GAG chains are also important for the interaction with the GAG-binding proteins including ATIII or receptor-type protein tyrosine phosphatase PTPRσ (2,6). Therefore, GAG biosynthesis by glycosyltransferases, sulfotransferases, and C5 epimerase is intricately regulated at multiple levels in mammals as the degree of sulfation and GAG C5 epimerization are both tissue-and cell type-specific (7)(8)(9)(10)(11). There are several reports describing that the ratio of the 4-O-sulfation and 6-Osulfation (4S/6S) in CS disaccharides, changed during the normal embryonic development, growth, and aging (12)(13)(14)(15)(16).…”

Section: A Introductionmentioning

confidence: 99%

Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways

Higashi

2020

TIGG

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Glycosaminoglycans (GAGs), a group of structurally related acidic polysaccharides, are primarily present as glycan moieties of proteoglycans (PGs). The physiological functions of PGs depend on the interaction between the glycan moieties and proteins such as growth factors, chemokines, and adhesion molecules. For this reason, the sulfation pattern, the degree of epimerization, and the glycan moiety chain length impact their interactions with GAG-binding proteins. Although the structural changes in GAGs occur during the development and aging process, their detailed mechanisms are not fully understood. This review provides an overview of the heparan sulfate (HS)-and chondroitin sulfate (CS)-related gene expression at the transcriptional and translational level. In addition, it also describes the molecular mechanisms of the polyamine stimulation of glycosaminoglycan synthesis. HS biosynthesis was initiated once N-acetylglucosamine (GlcNAc) is transferred by EXTL3 to the common linkage tetrasaccharides, glucuronic acid (GlcA)β1-3galactose (Gal)β1-3Galβ1-4-xylose (Xyl)β1-O-Ser in PGs (19). Chain elongation is catalyzed by the EXT1/EXT2 heterodimer through the alternate addition of GlcNAc and GlcA residues (19). If GlcNAc is transferred to the linkage region by EXTL2, initiation of chain elongation is inhibited. HS backbone is epimerized and sulfated by

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“…Klf4 has a long GC-rich 5 0 -UTR, one of the characteristics of genes regulated by polyamines at the translational level. Several mechanisms of polyamine mediated stimulation of translation have been reported, such as ribosome shunting on the 5 0 -UTR [8], distant positioning of the CR sequence from the AUG [29], frameshifting at the termination codon (UGA) on the ORF [36], and miRNA mediated suppression of initiation codon recognition [37]. In this study, to clarify the mechanism of translational stimulation of KLF4 by polyamines, we used luciferase reporter plasmids containing several 5 0 -UTR versions of Klf4 mRNA.…”

Section: Discussionmentioning

confidence: 99%

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

et al. 2020

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Mast cells have secretory granules containing chemical mediators such as histamine and play important roles in the immune system. Polyamines are essential factors for cellular processes such as gene expression and translation. It has been reported that secretory granules contain both histamine and polyamines, which have similar chemical structures and are produced from the metabolism of cationic amino acids. We investigated the effect of polyamine depletion on mast cells using bone marrow-derived mast cells (BMMCs). Polyamine depletion was induced using α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. DFMO treatment resulted in a significant reduction of cell number and abnormal secretory granules in BMMCs. Moreover, the cells showed a 2.3-fold increase in intracellular histamine and up-regulation of histidine decarboxylase (HDC) at the transcriptional level during BMMC differentiation. Levels of the transcription factor kruppel-like factor 4 (KLF4) greatly decreased upon DFMO treatment; however, Klf4 mRNA was expressed at levels similar to controls. We determined the translational regulation of KLF4 using reporter genes encoding Klf4-luc2 fusion mRNA, for transfecting NIH3T3 cells, and performed in vitro translation. We found that the efficiency of KLF4 synthesis in response to DFMO treatment was enhanced by the existence of a GC-rich 5 0 -untranslated region (5 0 -UTR) on Klf4 mRNA, regardless of the recognition of the initiation codon. Taken together, these results indicate that the enhancement of histamine synthesis by DFMO depends on the up-regulation of Hdc expression, achieved by removal of transcriptional suppression of KLF4, during differentiation. OPEN ACCESS Citation: Nishimura K, Okamoto M, Shibue R, Mizuta T, Shibayama T, Yoshino T, et al. (2020) KLF4 is required for suppression of histamine synthesis by polyamines during bone marrowderived mast cell differentiation. PLoS ONE 15(2): e0229744. https://doi.

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Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2

Cited by 25 publications

References 62 publications

Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche

Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche

Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

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