PARP-1 Expression in the Mouse is Controlled by an Autoregulatory Loop: PARP-1 Binding to an Upstream S/MAR Element and to a Novel Recognition Motif in its Promoter Suppresses Transcription

Vidaković, Melita; Gluch, Angela; Jian, Qiao; Oumard, André; Frisch, Matthias; Poznanović, Goran; Bode, Jürgen

doi:10.1016/j.jmb.2009.03.032

Cited by 21 publications

(47 citation statements)

References 74 publications

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“…Inhibition of PARP activity by 3AB or PJ34 decreased TGF-β1-induced poly(ADP-ribosy)lation levels of proteins (Figure 1B). Activation of PARP1 increased expression of its own gene [18], [19]. In this study, treatment with 3AB or PJ34 prevented TGF-β1-induced increase in PARP1 expression (Figure 1C).…”

Section: Resultssupporting

confidence: 54%

“…Under basic condition, PARP1 is a transcriptional repressor of its own gene since it directly binds to the certain secondary structures or scaffold/matrix-attachment regions in the promoter to prevent gene transcription [18], [19]. Auto-poly(ADP-ribosy)lation prevents PARP1 binding to the promoter of its own gene and thereby increases the transcription of itself [18], [19]. Thereby, ROS induced auto-modification of PARP1 enhances PARP1 gene transcription.…”

Section: Discussionmentioning

confidence: 99%

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Poly(ADP-ribose) Polymerase 1 Is Indispensable for Transforming Growth Factor-β Induced Smad3 Activation in Vascular Smooth Muscle Cell

Huang

Wang

et al. 2011

PLoS ONE

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BackgroundTransforming growth factor type-β (TGF-β)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-β signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-β signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs).Methods and ResultsTGF-β1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-β1-induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-β1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-β1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Iα1, collagen IIIα1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs.ConclusionsPARP1 is indispensable for TGF-β1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-β/Smad3 pathway.

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Section: Resultssupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) Polymerase 1 Is Indispensable for Transforming Growth Factor-β Induced Smad3 Activation in Vascular Smooth Muscle Cell

Huang

Wang

et al. 2011

PLoS ONE

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“…Therefore, it is possible that MMP-9 and other proteins (including involucrin) could be involved in this type of transcriptional regulation by PARP-1. In this respect, the GCCT-complementary AGGC sequence is common to KRE-M9 in the MMP-9 promoter and to KRE-4 in the involucrin promoter out of the AGGCC-complementary GGCCT motif reported in the PARP-1 promoter itself [50].…”

Section: Discussionmentioning

confidence: 92%

“…In addition, there have been reports indicating its additional roles in the transcriptional regulation of specific proteins [42][43][44][45][46][47][48][49][50][51]. In such cases, other than by its catalytic activity of poly ADPribosylation [43,44] or as a co-regulator [43,51], transcriptional regulation by PARP-1 due to its ability to directly bind to specific DNA sequences has been reported and is confirmed in this study [45][46][47][48][49][50]. Therefore, it is possible that MMP-9 and other proteins (including involucrin) could be involved in this type of transcriptional regulation by PARP-1.…”

Section: Discussionmentioning

confidence: 99%

Suppression of matrix metalloproteinase-9 expression in undifferentiated, non-apoptotic keratinocytes is abrogated by the cleavage of poly(ADP-ribose) polymerase-1

Kobayashi

2011

Apoptosis

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Matrix metalloproteinase (MMP)-9, an enzyme that degrades the extracellular matrix, has been implicated as a key enzyme in the process of tissue remodeling. This study demonstrates the regulation of MMP-9 transcription through a gene regulatory element in its promoter (the KRE-M9 element). The KRE-M9-binding protein was purified and identified as poly(ADP-ribose) polymerase-1 (PARP-1), which inhibits the transcription of MMP-9 similar to involucrin. This regulation occurs in non-apoptotic keratinocytes using the distinctive culture conditions of high and low Ca(2+) levels. PARP cleavage, which occurs during apoptosis, results in de-repression of MMP-9 promoter activity. These data clarify a new role of PARP-1 and suggest a physiologically relevant connection between caspase activation and MMP-9 expression.

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“…Under physiological conditions, PARP1 ADP-ribosylation activity curiously follows the rhythmic circadian cycle [148]. The mechanism governing oscillating PARP1 enzymatic activity is not known, although in mice, autoregulatory loops with PARP1 acting as a transcriptional repressor at its own promoter may help to achieve this [149]. Rhythmic cycling of PARP1 ADP-ribosylation activity predicts for temporally compartmentalized DNA repair and transcription factor functions, where the efficacies of each is conversely related and differs throughout the day in a circadian rhythm-dependent manner (Figure 4).…”

Section: Dysregulated Parp1 Adp-ribosylation and Transcription Actmentioning

confidence: 99%

Functional Aspects of PARP1 in DNA Repair and Transcription

2012

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Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP-ribosylating enzyme essential for initiating various forms of DNA repair. Inhibiting its enzyme activity with small molecules thus achieves synthetic lethality by preventing unwanted DNA repair in the treatment of cancers. Through enzyme-dependent chromatin remodeling and enzyme-independent motif recognition, PARP1 also plays important roles in regulating gene expression. Besides presenting current findings on how each process is individually controlled by PARP1, we shall discuss how transcription and DNA repair are so intricately linked that disturbance by PARP1 enzymatic inhibition, enzyme hyperactivation in diseases, and viral replication can favor one function while suppressing the other.

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PARP-1 Expression in the Mouse is Controlled by an Autoregulatory Loop: PARP-1 Binding to an Upstream S/MAR Element and to a Novel Recognition Motif in its Promoter Suppresses Transcription

Cited by 21 publications

References 74 publications

Poly(ADP-ribose) Polymerase 1 Is Indispensable for Transforming Growth Factor-β Induced Smad3 Activation in Vascular Smooth Muscle Cell

Poly(ADP-ribose) Polymerase 1 Is Indispensable for Transforming Growth Factor-β Induced Smad3 Activation in Vascular Smooth Muscle Cell

Suppression of matrix metalloproteinase-9 expression in undifferentiated, non-apoptotic keratinocytes is abrogated by the cleavage of poly(ADP-ribose) polymerase-1

Functional Aspects of PARP1 in DNA Repair and Transcription

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