PARP-1 Attenuates Smad-Mediated Transcription

Lönn, Peter; Heide, Lars P. van der; Dahl, Markus; Hellman, Ulf; Heldin, Carl‐Henrik; Moustakas, Aristidis

doi:10.1016/j.molcel.2010.10.029

Cited by 126 publications

(134 citation statements)

References 26 publications

(40 reference statements)

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“…38 As another typical example, PARP1 can dissociate Smad complexes from DNA through poly(ADP-ribosyl)ating Smad3 and Smad4, therefore attenuating Smad-mediated transcription and inhibiting TGF-β-induced epithelial-mesenchymal transition (EMT). 39 Since we have demonstrated before the function of Snail-LSD1 on E-cadherin suppression and EMT induction, there is also a possibility that PARP1 participates in this regulation process. In contrast to the Smad-PARP1 model, however, poly(ADP-ribosyl)ation of Snail by PARP1 would rather enhance the inhibitory effect of Snail-LSD1 on E-cadherin and promote EMT.…”

Section: Discussionmentioning

confidence: 89%

Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

2014

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Section: Discussionmentioning

confidence: 89%

Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

2014

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“…As an increasing number of studies have shown, PAR can be accumulated in normal, steady-state, or basal conditions (e.g., during hormonal signaling, certain stages of development, circadian clock function, and mitosis) without triggering stress responses (Tulin and Spradling 2003;Bai et al 2007;Chang et al 2009;Asher et al 2010;Lonn et al 2010;Geistrikh et al 2011;Rouleau et al 2011;Yoo et al 2011;Erener et al 2012). How does the cell interpret PAR accumulation as a stress signal in one circumstance, but not another?…”

Section: Parp-and Par-dependent Processes In Normal Conditions?mentioning

confidence: 99%

On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1

Luo¹,

Kraus²

2012

Genes Dev.

624

607

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Cellular stress responses are mediated through a series of regulatory processes that occur at the genomic, transcriptional, post-transcriptional, translational, and posttranslational levels. These responses require a complex network of sensors and effectors from multiple signaling pathways, including the abundant and ubiquitous nuclear enzyme poly(ADP-ribose) (PAR) polymerase-1 (PARP-1). PARP-1 functions at the center of cellular stress responses, where it processes diverse signals and, in response, directs cells to specific fates (e.g., DNA repair vs. cell death) based on the type and strength of the stress stimulus. Many of PARP-1's functions in stress response pathways are mediated by its regulated synthesis of PAR, a negatively charged polymer, using NAD + as a donor of ADP-ribose units. Thus, PARP-1's functions are intimately tied to nuclear NAD + metabolism and the broader metabolic profile of the cell. Recent studies in cell and animal models have highlighted the roles of PARP-1 and PAR in the response to a wide variety of extrinsic and intrinsic stress signals, including those initiated by oxidative, nitrosative, genotoxic, oncogenic, thermal, inflammatory, and metabolic stresses. These responses underlie pathological conditions, including cancer, inflammation-related diseases, and metabolic dysregulation. The development of PARP inhibitors is being pursued as a therapeutic approach to these conditions. In this review, we highlight the newest findings about PARP-1's role in stress responses in the context of the historical data.Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is the most abundant and ubiquitous member of a family of 17 related mammalian proteins. Studies over the past two decades, complemented by some exciting recent reports, have begun to crystallize a clearer view of one of the most robust and consistent functions of PARP-1 across biological systems: as a stress sensor and a stress response mediator. In this review, we highlight the newest findings in this area in the context of the historical data. We did not attempt to provide a comprehensive review, but rather opted to focus on key findings that have clarified the role of PARP-1 (and related PARPs) in stress responses. The reader is directed to a variety of other excellent reviews that cover other aspects of PARP-1 biology (D

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“…It was proposed that acetylation of Lys19 in SMAD2Dexon3 promotes DNA binding by releasing the MH1 domain from this inhibitory interaction. Another posttranslational modification that regulates DNA binding of SMAD3 -SMAD4 complexes is poly-ADP-ribosylation (PARylation), which is induced by poly(ADP-ribose) polymerase-1 (PARP1) (Lönn et al 2010). Both SMAD3 and SMAD4 were found to be PARylated, and in SMAD3, the sites of PARylation were mapped to Glu50 and Glu52 in the MH1 domain.…”

Section: Dna Binding Of Smad Complexes and Its Regulation By Posttranmentioning

confidence: 99%

Transcriptional Control by the SMADs

Hill

2016

Cold Spring Harb Perspect Biol

282

256

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The transforming growth factor-b (TGF-b) family of ligands elicit their biological effects by initiating new programs of gene expression. The best understood signal transducers for these ligands are the SMADs, which essentially act as transcription factors that are activated in the cytoplasm and then accumulate in the nucleus in response to ligand induction where they bind to enhancer/promoter sequences in the regulatory regions of target genes to either activate or repress transcription. This review focuses on the mechanisms whereby the SMADs achieve this and the functional implications. The SMAD complexes have weak affinity for DNA and limited specificity and, thus, they cooperate with other site-specific transcription factors that act either to actively recruit the SMAD complexes or to stabilize their DNA binding. In some situations, these cooperating transcription factors function to integrate the signals from TGF-b family ligands with environmental cues or with information about cell lineage. Activated SMAD complexes regulate transcription via remodeling of the chromatin template. Consistent with this, they recruit a variety of coactivators and corepressors to the chromatin, which either directly or indirectly modify histones and/or modulate chromatin structure.

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PARP-1 Attenuates Smad-Mediated Transcription

Cited by 126 publications

References 26 publications

Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent manner

On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1

Transcriptional Control by the SMADs

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