PARP-1: a new player in the asthma field?

Szabó, Éva; Kovács, István; Grune, Tilman; Haczku, Angela Franciska; Virág, László

doi:10.1111/j.1398-9995.2011.02551.x

Cited by 13 publications

(11 citation statements)

References 19 publications

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“…Thereby, poly-ADP-ribosylation plays a major role in a multitude of biological processes, such as maintenance of genomic stability, chromatin modification, cell death and transcriptional regulation. These observations also implicate ARTD1 in different pathologies such as cancer, inflammation and neurodegenerative disorders [1,9,10].…”

Section: Adp-ribosyltransferase Diphtheria Toxin-like 1 (Artd1)mentioning

confidence: 97%

ADP‐ribosylation of histones by ARTD1: An additional module of the histone code?

Hottiger

2011

FEBS Letters

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a b s t r a c t ADP-ribosylation is a covalent post-translational protein modification catalyzed by ADP-ribosyltransferases and is involved in important processes such as cell cycle regulation, DNA damage response, replication or transcription. Histones are ADP-ribosylated by ADP-ribosyltransferase diphtheria toxin-like 1 at specific amino acid residues, in particular lysines, of the histones tails. Specific ADP-ribosyl hydrolases and poly-ADP-ribose glucohydrolases degrade the ADP-ribose polymers. The ADP-ribose modification is read by zinc finger motifs or macrodomains, which then regulate chromatin structure and transcription. Thus, histone ADP-ribosylation may be considered an additional component of the histone code. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.1. ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1) ADP-ribosylation is a post-translational modification that is characterized by the synthesis of negatively charged polymers of ADP-ribose at specific acceptor amino acid residues of proteins. The synthesis of poly-ADP-ribose is catalyzed by ADPribosyltransferases (ARTs) and requires nicotinamide adenine dinucleotide (NAD + ) as a substrate [1]. The protein family of ARTs currently comprises 22 human enzymes with an ADP-ribosyltransferase domain [2]. The best characterized ART of the diphtheria toxin-like subclass, ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1/formally called PARP1), is an abundant chromatin associated nuclear protein of 113 kDa [2] that is implicated in crucial processes such as transcriptional control, cell differentiation or cell cycle regulation [3,4]. As for most ARTDs, the catalytic domain that catalyzes poly-ADP-ribosylation is located at the carboxylterminus of ARTD1 [2]. The N-terminal DNA-binding domain of ARTD1 is involved in the binding of different forms of nucleic acids and contains two zinc fingers, a third zinc binding motif and a nuclear localization signal [3]. Binding of this domain to DNA induces a strong interaction with the catalytic domain increasing the V max and decreasing the K m for NAD + of ARTD1 [5]. ARTD1 is both the main nuclear ART in mammalian cells as well as the main acceptor of poly-ADP-ribose in the cell [3,6]. The central auto-modification domain (AMD) contains acceptor amino acids for the covalent attachment of poly-ADP-ribose [5]. Three lysine residues in this ADM (K498, K521 and K524, called KTR) as well as additional residues within the 214 N-terminal amino acids were recently identified as the auto-ADP-ribosylation sites of ARTD1 [5]. Besides ARTD1, several other nuclear proteins (e.g. histones or transcription factors) are poly-ADP-ribosylated and thus functionally regulated by ARTD1 [7,8]. Thereby, poly-ADP-ribosylation plays a major role in a multitude of biological processes, such as maintenance of genomic stability, chromatin modification, cell death and transcriptional regulation. These observations also implicate ARTD1 in different pathologies such as cancer, inflamm...

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Section: Adp-ribosyltransferase Diphtheria Toxin-like 1 (Artd1)mentioning

confidence: 97%

ADP‐ribosylation of histones by ARTD1: An additional module of the histone code?

Hottiger

2011

FEBS Letters

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“…After binding to Hsp70, an (partially) unfolded substrate may either refold into native conformation and is released or remains bound to 20S, kept in a soluble state, unable to form aggregates with other unfolded proteins. Interestingly, in phases of stress detachment of the 19S regulator cap from the 20S “core” proteasome is mediated by Hsp70 binding to the 19S, resulting in a decline of 26S-proteolytic capacity, while the pool of free 20S is increased resulting in enhanced degradation of unfolded proteins [123].…”

Section: Proteostasis In Agingmentioning

confidence: 99%

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

et al. 2017

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Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.

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“…Cytokines are a category of potential targets for asthma. Their abnormal quantity during asthma attack made them to consider as potential targets 4 . Among the cytokines, interleukin 4, interleukin 5, interleukin 10, interleukin 13, interleukin 12 were identified as significant targets for the disease pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Comparative Study on Janus Kinase Enzyme activity of Pomegranate Leaf Extract and its Active Component Ellagic Acid for Asthma

Sarithamol¹,

Pushpa²,

Manoj³

2018

Orient. J. Chem

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Asthma is the most severe condition of lung airway inflammatory cells. Two third of asthmatic patients are nonresponsive towards existing treatments. The present study has focused on potency of IL4-JAK1-STAT6 signaling pathway as an investigational therapeutic target for the disease. Pomegranate plant is well studied for its potential phytochemicals. The therapeutic efficiency of pomegranate plant leaves and its active component ellagic acid against the signaling pathway has been investigated. The quantitative estimation of ellagic acid in the aqueous alcoholic extract of pomegranate leaves was done. Cell toxicity of ellagic acid and plant leaf extract was checked on macrophage raw cells using MTT assay and their activity against JAK1 enzyme were found out by ELISA method. The result signifies that pomegranate leaf extract is more efficient than ellagic acid towards JAK1 enzyme. Therefore the present study has highlighted the potency of pomegranate leaf extract over ellagic acid, the active component, for the disease asthma through IL4-JAK1-STAT6 pathway.

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PARP-1: a new player in the asthma field?

Cited by 13 publications

References 19 publications

ADP‐ribosylation of histones by ARTD1: An additional module of the histone code?

ADP‐ribosylation of histones by ARTD1: An additional module of the histone code?

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

Comparative Study on Janus Kinase Enzyme activity of Pomegranate Leaf Extract and its Active Component Ellagic Acid for Asthma

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