Characterization of sPARP-1

Sallmann, Frédéric R.; Vodenicharov, Momchil D.; Wang, Zhaoqi; Poirier, Guy G.

doi:10.1074/jbc.275.20.15504

Cited by 69 publications

(15 citation statements)

References 57 publications

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“…Another family member, PARP-2, has been shown to bind to and be activated by DNA strand breaks, although this protein lacks the classical zinc finger DNA-binding domain of PARP-1 (45). Finally, sPARP-1, although lacking a DNA-binding domain, can be activated by DNA damage (29). In this study, we have only been able to detect one NAD-dependent ADP-ribosyltransferase species capable of self-poly(ADP-ribosyl)ation in BJ/TERT and MCF-7 cells, namely PARP-1.…”

Section: Discussionmentioning

confidence: 59%

“…Retention of PARP activity is not the result of compensatory PARP enzymes such as sPARP-1, observed in PARP-1 Ϫ/Ϫ mouse embryo fibroblasts (29), because PARP-1 is the only NAD-dependent poly(ADP-ribosyl)ating enzyme detected in BJ/TERT cells. Rather, it may be the result of insufficient DBD expression in the clones.…”

Section: Timementioning

confidence: 99%

“…Purified bovine PARP-1 was included as a positive control. It has been previously shown that normal mouse embryo fibroblasts have two active poly(ADP-ribosyl)ating species; a major active band corresponding to the 113-kDa PARP-1 and a second active band with an approximate molecular mass of 60 kDa corresponding to sPARP-1 (29). In contrast, the human cell lines BJ/TERT and MCF-7 express only one protein species capable of NAD ϩ -dependent self-poly(ADP-ribosyl)ation in the presence of DNA strand breaks, provided by the DNase I-activated calf thymus DNA (Fig.…”

Section: Human Mcf-7 and Bj/tert Cells Express A Single Species With mentioning

confidence: 99%

“…Other studies employing dominant negative PARP-1 mutants (23), and PARP-1 knockout mice (24 -27) have yielded confusing and apparently conflicting data. Studies using certain PARP-1-deficient mouse cells are confounded by the fact that these cells retain poly(ADP-ribosyl)ation activity (28,29). Thus, although PARP-1 plays a clear role in the maintenance of genomic integrity, the functional relationship between PARP-1 and p53 remains unclear.…”

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confidence: 99%

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Poly(ADP-ribose) Polymerase-1 Is a Positive Regulator of the p53-mediated G1 Arrest Response following Ionizing Radiation

Wieler

Gagné²,

Vaziri

et al. 2003

Journal of Biological Chemistry

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103

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The p53 tumor suppressor protein plays a critical role in the cellular response to DNA damage leading to cell cycle arrest or apoptosis depending on cell type, culture conditions, and the extent of DNA damage. Loss of the p53-dependent DNA damage response can lead to genomic instability and the survival of cells carrying mutations and carcinogenic lesions thereby contributing to malignancy (1). DNA strand breaks produced by ionizing radiation (IR) 1 or by DNA repair intermediates following treatment with UV radiation or chemotherapeutic agents result in the accumulation of p53 protein and in the activation of its transcriptional activity (reviewed in Refs. 2 and 3). Elevated levels of p53 protein are believed to be important to initiate the events that lead to G 1 arrest or apoptosis after DNA damage. There is compelling evidence that post-translational modification of p53 is required for its stabilization, as well as for activation of its latent sequence-specific DNA-binding and transactivation functions. Once p53 becomes activated it binds as a tetramer to p53 responsive elements on double stranded DNA consisting of two half-sites (5Ј-PuPuPuC(A/T)(T/A)GPyPyPy-3Ј) separated by a spacer consisting of 0 -13 nucleotides (4). The site-specific DNA-binding activity of p53 leads to transcriptional activation of p53 target genes. Covalent modification of p53 has also been shown to regulate its subcellular localization, tetramerization, interaction with other proteins, and degradation. p53 protein is modified in vivo through phosphorylation, acetylation, poly(ADP-ribosyl)ation, ubiquitination, and sumoylation reactions (reviewed in Refs. 2 and 5).The events upstream of p53 activation are complex and not well understood. Several DNA damage sensory molecules are believed to relay the DNA damage signal to p53; each may be involved in the response to one or more types of DNA damage. For example, ataxia-telangiectasia-mutated kinase protein is involved in the activation of p53 in response to IR (6, 7), and ataxia telangiectasia-related kinase protein is involved in the activation of p53 in response to UV irradiation (8).Poly(ADP-ribose) polymerase (PARP-1) is an abundant nuclear enzyme that binds to, and is activated by, DNA single and double strand breaks (reviewed in Refs. 9 -11). Its activation represents one of the earliest responses to DNA damage in the cell. PARP-1 catalyzes the sequential transfer of ADP-ribose monomers onto nuclear protein acceptors using NAD ϩ as substrate. During the process of poly(ADP-ribosyl)ation, NAD ϩ is hydrolyzed and released as free nicotinamide. More than 30 nuclear proteins have been identified as poly(ADP-ribose) (pADPr) acceptors, with PARP-1 itself being the major target, via its automodification domain. pADPr acceptor proteins may be modified through covalent as well as through non-covalent association with pADPr, either free or bound to PARP-1. Poly-(ADP-ribose) glycohydrolase is the major enzyme responsible for the hydrolysis of pADPr. There is general agreement, based on genetic ...

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Section: Discussionmentioning

confidence: 59%

Section: Timementioning

confidence: 99%

Section: Human Mcf-7 and Bj/tert Cells Express A Single Species With mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Poly(ADP-ribose) Polymerase-1 Is a Positive Regulator of the p53-mediated G1 Arrest Response following Ionizing Radiation

Wieler

Gagné²,

Vaziri

et al. 2003

Journal of Biological Chemistry

Self Cite

103

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show abstract

“…In addition, PARP-1 can regulate its protein and DNA interactions by catalyzing its automodification with multiple PAR molecules. An alternative product of the PARP-1 gene is sPARP-1, a 55.3-kDa protein with nuclear localization and sequence identity to the catalytic domain of PARP-1 (4). It is also activated by DNA damaging agents but apparently does not require DNA strand breaks for activation.…”

mentioning

confidence: 99%