Tumor promoter phorbol-12-myristate-13-acetate induces poly(ADP)-ribosylation in fibroblasts.

Singh, Neeta; Poirier, Guy G.; Cerutti, Peter

doi:10.1002/j.1460-2075.1985.tb03807.x

Cited by 47 publications

(7 citation statements)

References 25 publications

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“…PARP-1 is predominantly nuclear whereas PARG is preferentially cytoplasmic, although a significant proportion is found in the nucleus (Winstall et al, 1999;Ohashi et al, 2003;Bonicalzi et al, 2003). DNA-damage-induced poly(ADP-ribose) is detected within minutes, peaks by 30 minutes and returns to basal levels 15-60 minutes later (Singh et al, 1985;Tartier et al, 2003). Similar kinetics of synthesis/degradation are also observed during transcription of the hsp70 locus in Drosophila (Tulin and Spradling, 2003).…”

Section: Poly(adp-ribose) Glycohydrolase and Chromatin Recondensationmentioning

confidence: 76%

Poly(ADP-ribosyl)ated chromatin domains: access granted

Rouleau

Aubin

Poirier

2004

Journal of Cell Science

177

153

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The seemingly static architecture of interphase and mitotic chromatin betrays an otherwise elegantly dynamic entity capable of remodelling itself to facilitate DNA replication, transcription, repair and recombination. Remodelling of local chromatin domains in response to physiological cues proceeds, at least in part, through transient cycles of relaxation and condensation that require use of histone variants and post-translational modifications of histones. Studies have connected poly(ADP-ribosyl)ation of histones with virtually every aspect of DNA metabolism and function over the years, most notably with the response to DNA damage, where convincing evidence supports its essential role granting repair machinery access to damaged DNA. Recent reports extend this notion to transcription and the maintenance of genomic stability, thereby supporting a general role for nuclear poly(ADPribosyl)ation in many aspects of genomic activity. The phenomenon might contribute to the 'histone code' by dictating levels of local chromatin compaction.

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Section: Poly(adp-ribose) Glycohydrolase and Chromatin Recondensationmentioning

confidence: 76%

Poly(ADP-ribosyl)ated chromatin domains: access granted

Rouleau

Aubin

Poirier

2004

Journal of Cell Science

177

153

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“…Since in this case the mechanism of activation of poly(ADP-ribose) synthase is possibly divergent from that assumed for the alkylation-mediated stimulation of poly(ADP-ribose) synthesis [64], it is noteworthy that very similar proteins were found to serve as major acceptors. Furthermore, recent studies applying a new technique to label endogenous poly(ADP-ribose) -protein conjugates specifically in growing human colon adenocarcinoma cells 1651 revealed that the label was preferentially incorporated into peptides with electrophoretic mobilities similar to histones and to poly(ADP-ribose) synthase, suggesting that modification of these acceptors might be of more general significance.…”

Section: Discussionmentioning

confidence: 86%

Poly(ADP-ribose) synthase is the major endogenous nonhistone acceptor for poly(ADP-ribose) in alkylated rat hepatoma cells

Adamietz

1987

Eur J Biochem

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The endogenous poly(ADP-ribosyl) -nonhistone protein conjugates were isolated from dimethyl-sulfatetreated rat hepatoma AH 7974 cells using aminophenylboronic-acid -agarose chromatography. Seven major components could be discerned on dodecyl sulfate gels (molecular mass 43,60,66, 86, 100, 110 and 170 kDa) while control cells indicated only slight staining at above 200 kDa. The most abundant conjugate formed in response to alkylation damage was further purified using preparative gel electrophoresis and identified on the basis of its intrinsic enzymic activity as automodified poly(APD-ribose) synthase. In addition, topoisomerase I activity was found associated with a 60-kDa peptide. ADP-ribosylated endonucleases and actin were not detectable. The purified conjugate fraction contained maximally 8.8 nmol/mg ADP-ribose and 7.9 nmol/mg oligo(ADPribose) with a mean chain length of 2.3 residues. The modifying (ADP-ribosyl), groups were attached to its acceptors by a hydroxylamine-insensitive bond and had practically no effect on the DNA affinity of either poly(ADP-ribose) synthase or topoisomerase I.Fragmentation of cellular DNA as induced by chemical or physical stress enhances the endogenous synthesis of poly(ADP-ribose) in the eucaryotic cell (for reviews see [l-31). The poly(ADP-ribose) synthase responsible for this reaction is capable of transferring the ADP-ribose moiety from the substrate NAD to a variety of chromosomal acceptor proteins with subsequent elongation to linear and branched homopolymers [4]. Formation of these products has been related to the regulation of several chromatin functions, especially those including intermediate nicking and resealing of DNA strands [5], such as cellular differentiation [6-91 and the DNA repair reactions [lo -131. The activity of the purified synthase was found to be completely dependent on binding to broken DNA [14] and inhibitors of the enzyme proved to be co-cytostatic [ l l , 15, 161 and co-carcinogenic [17-201 with DNA-damaging agents. These biological effects are apparently restricted to dividing cells, suggesting that poly(ADPribose) metabolism is required for the recovery of damaged cells progressing through the cell cycle but not for reactions directly involved in DNA excision repair [21,22]. Accordingly, inhibitors of poly(ADP-ribose) synthesis did not affect the rate of DNA ligation in alkylated HeLa cells [23,24] or mouse embryo fibroblasts [21], whereas strand-break frequency was enhanced and some breaks appeared to remain unrepaired in the absence of poly(ADP-ribose) synthesis. The molecular mechanism by which poly(ADP-ribose) can prevent alkylation-induced cell death ist still not understood. A frequent explanation is that poly(ADP-ribose) may regulate cellular events by directy modulating the enzymic activities of the modified proteins [5] in analogy to the action of extranuclear mono(ADP-ribosyl) transferases [3]. This view relies on the observation that poly(ADP-ribosy1)ation inhibits the activities of many nuclear enzymes in vitro: Ca2+/Mg2-dependent ...

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“…DMBA has been shown to bind to DNA and cause mutations particularly in the H-ras gene, which is normally involved with proliferation and differentiation (36). The tumor promoter TPA triggers ROS production and causes hyperplasia in skin cells with H-ras mutations, which leads ultimately to the formation of papillomas (36,37). CR is protective against the promotion phase of the two-stage carcinogenesis model and decreases tumor incidence and multiplicity (38).…”

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confidence: 99%

Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Pearson

Lewis

Price

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

214

156

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Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogendetoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR.aging ͉ carcinogenesis ͉ oxidative stress

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Tumor promoter phorbol-12-myristate-13-acetate induces poly(ADP)-ribosylation in fibroblasts.

Cited by 47 publications

References 25 publications

Poly(ADP-ribosyl)ated chromatin domains: access granted

Poly(ADP-ribosyl)ated chromatin domains: access granted

Poly(ADP-ribose) synthase is the major endogenous nonhistone acceptor for poly(ADP-ribose) in alkylated rat hepatoma cells

Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

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