The roles of PARP1 in gene control and cell differentiation

Ji, Yingbiao; Tulin, Adrian

doi:10.1016/j.gde.2010.06.001

Cited by 139 publications

(110 citation statements)

References 56 publications

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“…PARP1 post-translationally modifies histones H1 by poly(ADP-ribosyl)ation and modulates gene transcription. [20][21][22] However, the inhibition of basal PARP1 activity was sufficient to increase endogenous E2F1 activity monitored by transiently transfected E2A-Luc vector (see Figure 1). Therefore, we assumed that PARP1 might naturally poly(ADP-ribosyl)ate a non-histone protein on a naked E2F-sensitive gene promoter to inhibit its promoter activity.…”

Section: Resultsmentioning

confidence: 97%

“…The transcription factor E2F1 promotes cellcycle progression, but it also induces apoptosis during serum starvation. [5][6][7] Because PARP1 regulates gene transcription 21,22 and interacts directly with E2F1, 24 we tested whether PARP1 alters E2F1-dependent transcription. As the PARP1-deficient cell system, we used the Parp − / − 3T3 fibroblast line, together with its parental control line, the Parp +/+ 3T3 fibroblast cell line.…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, PARP1 acts as a regulatory component of multiprotein transcriptional complexes on the chromatin. 21,22 Because PARP1 is abundant in cancer cells, 23 PARP1 inhibition might counterbalance the oncogenic potential of cancer cells by reprogramming the transcriptional profiles of PARP1-modified genes. Consistent with this premise, PARP1 physically interacts with several cancerrelated transcription factors, including E2F1.…”

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confidence: 99%

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Regulation of E2F1-induced apoptosis by poly(ADP-ribosyl)ation

et al. 2014

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The transcription factor adenovirus E2 promoter-binding factor (E2F)-1 normally enhances cell-cycle progression, but it also induces apoptosis under certain conditions, including DNA damage and serum deprivation. Although DNA damage facilitates the phosphorylation and stabilization of E2F1 to trigger apoptosis, how serum starvation renders cells vulnerable to E2F1-induced apoptosis remains unclear. Because poly(ADP-ribose) polymerase 1 (PARP1), a nuclear enzyme essential for genomic stability and chromatin remodeling, interacts directly with E2F1, we investigated the effects of PARP1 on E2F1-mediated functions in the presence and absence of serum. PARP1 attenuation, which increased E2F1 transactivation, induced G 2 /M cell-cycle arrest under normal growth conditions, but enhanced E2F1-induced apoptosis in serum-starved cells. Interestingly, basal PARP1 activity was sufficient to modify E2F1 by poly(ADP-ribosyl)ation, which stabilized the interaction between E2F1 and the BIN1 tumor suppressor in the nucleus. Accordingly, BIN1 acted as an RB1-independent E2F1 corepressor. Because E2F1 directly activates the BIN1 gene promoter, BIN1 curbed E2F1 activity through a negative-feedback mechanism. Conversely, when the BIN1-E2F1 interaction was abolished by PARP1 suppression, E2F1 continuously increased BIN1 levels. This is functionally germane, as PARP1-depletionassociated G 2 /M arrest was reversed by the transfection of BIN1 siRNA. Moreover, PARP-inhibitor-associated anti-transformation activity was compromised by the coexpression of dominant-negative BIN1. Because serum starvation massively reduced the E2F1 poly(ADP-ribosyl)ation, we conclude that the release of BIN1 from hypo-poly(ADP-ribosyl)ated E2F1 is a mechanism by which serum starvation promotes E2F1-induced apoptosis.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of E2F1-induced apoptosis by poly(ADP-ribosyl)ation

et al. 2014

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“…Mer- (15). PARP aktivasyonunun ilişkili olduğu bazı olaylar Tablo 2'de sunulmuştur (16,17). DNA hasarı yapan kimyasallar, radyasyon, peroksidasyon PARP-1'in uyarılmasına neden olur.…”

Section: Poli (Adp-riboz) Polimerazlar (Parp'lar)unclassified

A New Approach in Cancer Treatment: Poly(ADP-Ribose) Polymerase-1 Inhibitors

Tok¹,

Kaymakçıoğlu²

2015

MUSBED

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Kanser tedavisinde yeni bir yaklaşım: Poli (ADP-riboz) polimeraz-1 inhibitörleri Genetik materyal olan DNA'da iç ve dış etkenler sonucu hasar oluşabilir. Normal bir hücrede bu hasarı onarabilecek çok sayıda tamir mekanizması vardır. Bunlardan biri de PARP-1 enzimidir. PARP-1, nikotinamid adenin dinükleotidden ADP-riboz yapılarını protein akseptörüne transfer eder. Böylece tek zincir DNA kırıkları onarılır. PARP-1'in inhibisyonu durumunda ise bu tek zincir DNA kırıkları onarılamaz ve çift zincir DNA kırıkları oluşur. Sonuçta hücre nekrozise ya da apoptozise gider. Kanser tedavisinde tümörlü hücrelerin PARP-1 inhibisyonuyla öldürülmesi amaçlanmaktadır. Bu amaçla son on yıl içinde çok sayıda çalışma yapılmış olup, günümüzde faz aşamasında bulunan ve piyasaya sürülmeyi bekleyen PARP-1 inhibitörleri mevcuttur. Bu derlemede, DNA'da oluşan hasarın hangi mekanizmalarla onarıldığı, PARP enzim ailesinin genomik bütünlüğü nasıl koruduğu ve kanser tedavisinde kullanılmak üzere geliştirilmiş PARP-1 inhibitörü kimyasal bileşiklerin yapıları hakkında bilgi verilmiştir.

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“…Nous avons démontré que le domaine BAR (bin amphiphysine rvs) de BIN1 interagit et inhibe le domaine central de PARP1, supprimant ainsi l'activité catalytique de l'enzyme [7] (Figure 2). Outre son rôle dans la réparation de l'ADN, PARP1 est aussi impliquée dans la régulation transcriptionnelle en servant de cofacteur à de multiples facteurs de transcription [9]. Ainsi, l'inhibition de l'activité de PARP1 par une interaction directe avec BIN1 pourrait non seulement réprimer le système de réparation de l'ADN, mais également être impliquée dans l'inhibition de la transactivation des gènes cibles de c-MYC.…”

Section: Implications Cliniquesunclassified

Un trio de choc pour pallier la chimiorésistance des cancers : c-MYC, PARP1, BIN1

Pyndiah

Sakamuro

2013

Med Sci (Paris)

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> Vaincre la résistance des cellules cancéreuses à la chimiothérapie est devenu un vrai défi en oncologie clinique. Cette résistance peut survenir dès les premières cures de chimiothérapie, sans phase de sensibilité initiale, témoignant d'une résistance intrinsèque des cellules. En revanche, la résistance acquise se traduit par une progression tumorale survenant secondairement, après une phase de grande chimiosensibilité. Les mécanismes moléculaires impliqués dans ces phénomènes de résistance ont été très étudiés au cours de ces dernières décennies. La dérégulation de gènes codant pour des protéines membranaires, comme le gène multi drug resistance (MDR) qui code pour des pompes d'efflux rejetant le médica-ment à l'extérieur de la cellule, réduit l'efficacité thérapeutique des molécules anticancéreuses [1]. Au niveau du foie, le MDR joue un rôle physiologique dans la détoxication cellulaire. Dans les cellules cancéreuses ayant acquis une résis-tance, le MDR est alors activé. Cependant, d'autres mécanismes de résistance existent probablement. Ainsi, certaines tumeurs possèdent des altérations spé-cifiques du système de réparation des dommages à l'ADN les rendant vulné-rables ou résistantes aux médicaments qui ont pour cible l'ADN. Par exemple, le système de réparation de l'ADN des cellules cancéreuses qui sont porteuses d'une mutation des gènes breast cancer 1 ou 2 (BRCA1 ou 2) est défectueux, ce qui rend ces cellules extrêmement sensibles aux agents intercalants de l'ADN et aux inhibiteurs de la poly-ADP-ribose polymérase (PARP) [2,3].

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The roles of PARP1 in gene control and cell differentiation

Cited by 139 publications

References 56 publications

Regulation of E2F1-induced apoptosis by poly(ADP-ribosyl)ation

Regulation of E2F1-induced apoptosis by poly(ADP-ribosyl)ation

A New Approach in Cancer Treatment: Poly(ADP-Ribose) Polymerase-1 Inhibitors

Un trio de choc pour pallier la chimiorésistance des cancers : c-MYC, PARP1, BIN1

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