Characterization of Poly(ADP-Ribose) Polymerase with Human Autoantibodies

Yamanaka, H; Ca, Penning; Eh, Willis; Db, Wasson; Da, Carson

doi:10.1007/978-1-4684-5676-9_38

Cited by 23 publications

(29 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, PARPs are almost entirely nuclear, having a diffuse nucleoplasmic distribution (40). By contrast, both TANK1 (27, 38) and TANK2 (Fig.…”

Section: Resultsmentioning

confidence: 93%

“…To determine whether TANK2-induced cell death had features of apoptosis or necrosis, we assessed the integrity of PARP1, which is cleaved shortly after apoptotic cell death is initiated (40,41). PARP1 remained intact up to 24 h after HT1080 cells were transfected with the TANK2 expression vector (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, it binds DNA sequences that anchor chromatin to the nuclear matrix (17). PARP1 is among the first proteins to be cleaved when cells undergo apoptosis (40,41), presumably in order to conserve ATP, which is required for apoptosis. Despite a wealth of information about PARP1 substrates and the consequences of germ line inactivation, there are still major gaps in our understanding of how PARP1 functions.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression

Kaminker

Kim

Taylor

et al. 2001

Journal of Biological Chemistry

200

169

View full text Add to dashboard Cite

Tankyrase (TANK1) is a human telomere-associated poly(ADP-ribose) polymerase (PARP) that binds the telomere-binding protein TRF1 and increases telomere length when overexpressed. Here we report characterization of a second human tankyrase, tankyrase 2 (TANK2), which can also interact with TRF1 but has properties distinct from those of TANK1. TANK2 is encoded by a 66-kilobase pair gene (TNKS2) containing 28 exons, which express a 6.7-kilobase pair mRNA and a 1166-amino acid protein. The protein shares 85% amino acid identity with TANK1 in the ankyrin repeat, sterile ␣-motif, and PARP catalytic domains but has a unique N-terminal domain, which is conserved in the murine TNKS2 gene. TANK2 interacted with TRF1 in yeast and in vitro and localized predominantly to a perinuclear region, similar to the properties of TANK1. In contrast to TANK1, however, TANK2 caused rapid cell death when highly overexpressed. TANK2-induced death featured loss of mitochondrial membrane potential, but not PARP1 cleavage, suggesting that TANK2 kills cells by necrosis. The cell death was prevented by the PARP inhibitor 3-aminobenzamide. In vivo, TANK2 may differ from TANK1 in its intrinsic or regulated PARP activity or its substrate specificity.Telomeres are the repetitive DNA sequences and specialized proteins that cap the ends of linear chromosomes and protect them from end-to-end fusion. In mammalian cells, loss or disruption of a telomere can cause cellular senescence, cell death, or genomic instability, depending on the genotype and cell context. A variety of events can lead to dysfunctional telomeres. Telomeres can be damaged directly by genotoxic agents and/or faulty DNA repair processes. In addition, the telomeric structure can be disrupted by changes in the expression or function of certain telomere-associated proteins. Finally, telomeres can erode owing to the biochemistry of DNA replication, which leaves 50 -200 bp 1 of 3Ј-telomeric DNA unreplicated upon completion of each S phase. Thus, in the absence of the enzyme telomerase, or another mechanism to replenish telomeric DNA, proliferating cells progressively lose telomeric DNA and eventually acquire one or more critically short or dysfunctional telomeres (1-3).Most normal mammalian cells respond to a critically short or dysfunctional telomere by undergoing cellular senescence (4 -7). This process results in an irreversible arrest of cell proliferation and striking changes in cell function (8). Dysfunctional telomeres can also induce apoptotic cell death, particularly in cells that harbor mutations in one or more cell cycle or DNA damage checkpoints (9 -11). Very little is known about how telomeres signal cells to undergo senescence or apoptosis. However, the recent discovery of a telomere-associated poly(ADPribose) polymerase (PARP) (12) provides a potential mechanism by which telomeres transmit signals to cellular proteins that regulate the senescence and apoptotic responses.PARPs catalyze the formation of branched chains of ADPribose polymers on selected proteins, using NAD ϩ ...

show abstract

“…Second, PARPs are almost entirely nuclear, having a diffuse nucleoplasmic distribution (40). By contrast, both TANK1 (27, 38) and TANK2 (Fig.…”

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression

Kaminker

Kim

Taylor

et al. 2001

Journal of Biological Chemistry

200

169

View full text Add to dashboard Cite

show abstract

“…Two other members of the PARP family, PARP-2 and PARP-3, also possess poly(ADP-ribose) polymerase activity (28). However, PARP-1 is thought to be the major contributor and responsible for over 90% of cellular PARylation (29,30). Thus, it is possible that PARP-1 is the major downstream mediator of FASN in the NHEJ repair of DSBs.…”

Section: Discussionmentioning

confidence: 99%

FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

Dong

Wang

et al. 2016

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

View full text Add to dashboard Cite

Fatty acid synthase (FASN), the sole cytosolic mammalian enzyme for de novo lipid synthesis, is crucial for cancer cell survival and associates with poor prognosis. FASN overexpression has been found to cause resistance to genotoxic insults. Here we tested the hypothesis that FASN regulates DNA repair to facilitate survival against genotoxic insults and found that FASN suppresses NF-κB but increases specificity protein 1 (SP1) expression. NF-κB and SP1 bind to a composite element in the poly(ADP-ribose) polymerase 1 (PARP-1) promoter in a mutually exclusive manner and regulate PARP-1 expression. Up-regulation of PARP-1 by FASN in turn increases Ku protein recruitment and DNA repair. Furthermore, lipid deprivation suppresses SP1 expression, which is able to be rescued by palmitate supplementation. However, lipid deprivation or palmitate supplementation has no effect on NF-κB expression. Thus, FASN may regulate NF-κB and SP1 expression using different mechanisms. Altogether, we conclude that FASN regulates cellular response against genotoxic insults by up-regulating PARP-1 and DNA repair via NF-κB and SP1.fatty acid synthase | transcription regulation | DNA repair | drug resistance | radiation resistance F atty acid synthase (FASN) is the key mammalian enzyme required for de novo synthesis of palmitate. FASN expression and activity are largely suppressed by sufficient dietary fat in most normal nonadipose tissues but are abnormally elevated in many human cancers and associated with poor prognosis (1). FASN association with poor prognosis may derive in part from FASN function in drug resistance during chemotherapy. Indeed, it has been found that FASN expression and/or activity was increased in drug-selected and -resistant breast (2) and pancreatic (3) cancer cells. It was also found that FASN overexpression causes cellular resistance to DNA-damaging drugs such as doxorubicin and mitoxantrone but not to microtubule modulators such as vinblastine and paclitaxel (4). Decreased ceramide production following doxorubicin treatment via suppression of tumor necrosis factor (TNF)-α production is believed to be one of the mechanisms of FASN-induced resistance to doxorubicin (4).The observation that FASN increases resistance to genotoxic drugs prompted us to hypothesize that FASN overexpression may up-regulate DNA damage response/repair pathways. In this study, we tested this hypothesis with a focus on the repair of DNA double-strand breaks (DSBs), which are commonly induced by the anticancer drugs doxorubicin and mitoxantrone and ionizing radiation. In mammalian cells, DSBs are repaired mainly via homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways. NHEJ is the predominant form of DSB repair because it occurs during all phases of the cell cycle whereas HR only initiates at late G1 and S phases (5). Hence, we examined NHEJ repair of DSBs and found that FASN up-regulates NHEJ activity and repair of DSBs by increasing poly(ADP-ribose) polymerase 1 (PARP-1) expression via increasing the expression of spec...

show abstract

“…The ADPRT protein is involved in genomic integrity since it regulates cellular response to DNA repair and apoptosis and has been shown to display a protective effect against cancer development (Burkle et al 2002;Masutani et al 2003). Although several additional PARPs are expressed in humans (Burkle 2005;Burkle et al 2005), ADPRT/PARP-1 is the founding family member, showing a high and wide expression in human cells (Yamanaka et al 1988;Ludwig et al 1988). Several years ago, it was suggested that the ADPRT gene is involved in Fanconi anemia (FA) (Schweiger et al 1987); however, no ADPRT abnormalities were found in FA patients of complementation group A (Flick et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Genetic sequence variations and ADPRT haplotype analysis in French Canadian families with high risk of breast cancer

et al. 2007

View full text Add to dashboard Cite

The poly(ADP-ribose) polymerase (PARP/ ADPRT) protein family catalyzes the synthesis of cellular poly(ADP-ribose) following DNA damage and is involved in genomic integrity by regulating cellular responses to DNA damage and apoptosis. Moreover, ADPRT inhibition contributes to a protective effect against cancer development. These findings render ADPRT an attractive candidate susceptibility gene for breast cancer, and thus the goal of this study was to evaluate the possible involvement of ADPRT sequence variations in breast cancer susceptibility. The complete sequence of the 23 exons and flanking intronic sequences of the ADPRT gene was analyzed in 54 affected individuals from distinct high-risk non-BRCA1/2 French Canadian families. No deleterious truncating mutation was identified in the coding region. However, 34 sequence variations were identified, among which seven are coding variants and seven are novel changes. All coding variants and intronic changes located in the vicinity of the coding variants identified in the case series were also analyzed in a cohort of 73 unrelated healthy French Canadian individuals. Interestingly, one missense variant (Pro377Ser) was observed in three different breast cancer cases but was not present among unaffected individuals. We have conducted here an exhaustive detailed mutation and haplotype tagging analysis of the ADPRT gene with regard to breast cancer, providing useful data for other large-scale association studies. Additional studies in other cohorts and other populations are however needed to further evaluate the implication of the Pro377Ser missense variant with regard to breast cancer susceptibility.

show abstract

Characterization of Poly(ADP-Ribose) Polymerase with Human Autoantibodies

Cited by 23 publications

References 13 publications

TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression

TANK2, a New TRF1-associated Poly(ADP-ribose) Polymerase, Causes Rapid Induction of Cell Death upon Overexpression

FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

Genetic sequence variations and ADPRT haplotype analysis in French Canadian families with high risk of breast cancer

Contact Info

Product

Resources

About