The Protein Zfand5 Binds and Stabilizes mRNAs with AU-rich Elements in Their 3′-Untranslated Regions

He, Guoan; Sun, Dongxu; Ou, Zhiying; Ding, Aihao

doi:10.1074/jbc.m112.362020

Cited by 17 publications

(16 citation statements)

References 53 publications

(58 reference statements)

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“…6B/C). Apart from TIS11 family proteins we also investigated mRNA expression of the recently discovered Zfand5, a protein stabilizing ARE-containing transcripts [13]. While we found a higher expression of Zfand5 transcript in RAW macrophages than in WT BMMCs that were either untreated or stimulated with LPS for 1 h, after 3 h of LPS treatment mRNA expression of Zfand5 was comparable between the different cell types (Fig.…”

Section: Resultsmentioning

confidence: 76%

“…Exemplarily, the ubiquitous nuclear protein HuR has been shown to bind to ARE-containing transcripts, thereby increasing their half-life [12]. HuR and the recently discovered ARE-binding protein Zfand5 bind to the AREs in the TNF-α mRNA, competitively counteracting the effect of TTP binding and thus leading to stabilization and enhanced translation of the TNF-α transcript [13, 14]. The balance between mRNA stabilizing and destabilizing proteins competing for the same ARE sites adds another layer of regulation to the overall translation of proteins.…”

Section: Introductionmentioning

confidence: 99%

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LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

Hochdörfer

Tiedje

Stumpo

et al. 2013

Cellular Signalling

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The production of the proinflammatory cytokines TNF-α and IL-6 is regulated by various mRNA-binding proteins, influencing stability and translation of the respective transcripts. Research in macrophages has shown the importance of the p38-MK2-tristetraprolin (TTP) axis for regulation of TNF-α mRNA stability and translation. In the current study we examined a possible involvement of p38 and TTP in LPS-induced cytokine production in bone marrow-derived mast cells (BMMCs). Using pharmacological inhibitors we initially found a strong dependence of LPS-induced TNF-α and IL-6 production on p38 activation, whereas activation of the Erk pathway appeared dispensable. LPS treatment also induced p38-dependent expression of the TTP gene. This prompted us to analyze the proinflammatory cytokine response in BMMCs generated from TTP-deficient mice. Unexpectedly, there were no significant differences in cytokine production between TTP-deficient and WT BMMCs in response to LPS. Gene expression and cytokine production of TNF-α and IL-6 as well as stability of the TNF-α transcript were comparable between TTP-deficient and WT BMMCs. In contrast to TTP mRNA expression, TTP protein expression could not be detected in BMMCs. While we successfully precipitated and detected TTP from lysates of LPS-stimulated RAW 264.7 macrophages, this was not accomplished from BMMC lysates. In contrast, we found mRNA and protein expression of the other TIS11 family members connected to regulation of mRNA stability, BRF1 and BRF2, and detected their interaction with 14-3-3 proteins. These data suggest that control of cytokine mRNA stability and translation in MCs is exerted by proteins different from TTP.

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Section: Resultsmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

Hochdörfer

Tiedje

Stumpo

et al. 2013

Cellular Signalling

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show abstract

“…Previous investigations have found that ZFAND2A expression is induced by arsenite (114,115) and heat shock (116). Similarly in macrophages, ZFAND5 expression is induced by cell stress in response to TNF, IFNg, LPS, and other toll-like receptor ligands (117)(118)(119). ZFAND5 also can compete with zinc finger protein 36 (aka tristetraprolin) and stabilizes class II adenylate/ uridine-rich sequence element containing mRNA, a region common to inflammatory mediator transcripts including TNF mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…ZFAND5 also can compete with zinc finger protein 36 (aka tristetraprolin) and stabilizes class II adenylate/ uridine-rich sequence element containing mRNA, a region common to inflammatory mediator transcripts including TNF mRNA. Thus, ZFAND5 is induced by and stabilizes TNF (119). However, the role of these proteins in ALI must be viewed with caution because structural similarity does not predict functional similarity.…”

Section: Discussionmentioning

confidence: 99%

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

Leikauf

Concel

Bein

et al. 2013

Am J Respir Cell Mol Biol

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In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that >10% of mice carried the minor allele and that this allele could account for >10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor b1 signaling, which previously has been associated with the susceptibility to ALI in mice.

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“…Сверхэкспрессия ZFAND5 делает клетки чувствительные к TNF-индуцированному апоптозу. Ген ZFAND5 может быть вовлечен в регуляцию активации NF-kappa-B и апоптоза [17]. Сверх экспрессия генов ZFAND5 и GREB1 делает клетки чувствительные к TNF-индуцированному апоптозу, который опосредуется каспазой 8 и 3, тогда как низкая экспрессия этих генов препятствует индукции программированной клеточной смерти.…”

Section: а) б)unclassified

Statistical Analysis of Radiation-Induced Dynamics of Cancer Cell Transcriptome Using Dna-Microarray Data

Sibatov¹

2013

Math.Biol.Bioinf.

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учебный корпус, ВМКАннотация. В работе проведён анализ данных ДНК-микрочипов по радиационно-индуцированной динамике транскриптома раковых клеток линии HCT116 с нормальным и мутантным геном ТР53. Транскриптом анализировался через 1, 12 и 24 часа после облучения с использованием микроматрицы Affymetrix серии HGU133А. Получено, что вероятностные характеристики разностей экспрессии существенно зависят от интенсивностей базового уровня, причем для абсолютных разностей эта зависимость нелинейная. Эффект учтён в рамках алгоритма «огибающая шума» на этапах фильтрации, кластеризации и группировки генов. Судить об эффективности применяемых в работе процедур обработки данных ДНК-микрочипов можно по результатам иерархической кластеризации и метода групповых средних. Для генов, прошедших процедуру фильтрации, построены дендрограммы, на основе которых проведено предварительное сравнение динамики ключевых сигнальных путей, связанных с программируемой клеточной смертью и репарацией ДНК. Ключевые слова: ДНК-микроматрица, экспрессия генов, иерархическая кластеризация, метод групповых средних. ВВЕДЕНИЕВ работе анализируются данные по радиационно-индуцированной динамике транскриптома раковых клеток на примере линии HCT116. Данные получены с помощью технологии ДНК-микроматриц [1][2][3][4][5][6][7][8]. Как известно, ДНК-микрочип представляет собой нанесённые на подложку в определенном порядке фрагменты одноцепочечных ДНК. Эти синтетические молекулы выступают в роли зондов. Меченные флуоресцентным красителем комплементарные цепи ДНК из исследуемого образца гибридизуются с зондами. Важнейшим шагом в анализе данных ДНК-микрочипов является расчёт уровня экспрессии генов по интенсивности свечения проб на чипе. Как известно, на интенсивность свечения проб влияет множество факторов. Избавление от эффектов технической вариации (связанной с выделением образцов, окрашиванием и гибридизацией) и ошибок измерения подразумевается на этапе предобработки данных ДНК-микроматриц. Предобработка подразумевает три последовательных стадии: фоновую поправку, нормализацию и суммаризацию.

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The Protein Zfand5 Binds and Stabilizes mRNAs with AU-rich Elements in Their 3′-Untranslated Regions

Cited by 17 publications

References 53 publications

LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

Statistical Analysis of Radiation-Induced Dynamics of Cancer Cell Transcriptome Using Dna-Microarray Data

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