Poly(ADP-ribose) polymerase: a guardian angel protecting the genome and suppressing tumorigenesis

Tong, Wei‐Min; Cortes, Ulrich; Wang, Zhaoqi

doi:10.1016/s0304-419x(01)00035-x

Cited by 107 publications

(105 citation statements)

References 117 publications

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“…Several proteins (6.6%) were arbitrarily regrouped into the class named "others" because they are involved in different biological processes, and each of them would require the construction of a novel specific functional class. For example, importin ␣-2 subunit, casein kinase II, ubiquitin, poly[ADP-ribose] polymerase-1, or S100 proteins are proteins from this category (Allende and Allende, 1995;Pickart, 2001;Tong et al, 2001;Weis et al, In addition, for each class, the number of proteins with a demonstrated involvement in the biological process is given, followed by the number of proteins with hypothetical involvement in this biological process in italics.…”

Section: Discussionmentioning

confidence: 99%

Functional Proteomic Analysis of Human Nucleolus

Scherl

Couté

Déon

et al. 2002

MBoC

445

378

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The notion of a “plurifunctional” nucleolus is now well established. However, molecular mechanisms underlying the biological processes occurring within this nuclear domain remain only partially understood. As a first step in elucidating these mechanisms we have carried out a proteomic analysis to draw up a list of proteins present within nucleoli of HeLa cells. This analysis allowed the identification of 213 different nucleolar proteins. This catalog complements that of the 271 proteins obtained recently by others, giving a total of ∼350 different nucleolar proteins. Functional classification of these proteins allowed outlining several biological processes taking place within nucleoli. Bioinformatic analyses permitted the assignment of hypothetical functions for 43 proteins for which no functional information is available. Notably, a role in ribosome biogenesis was proposed for 31 proteins. More generally, this functional classification reinforces the plurifunctional nature of nucleoli and provides convincing evidence that nucleoli may play a central role in the control of gene expression. Finally, this analysis supports the recent demonstration of a coupling of transcription and translation in higher eukaryotes.

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Section: Discussionmentioning

confidence: 99%

Functional Proteomic Analysis of Human Nucleolus

Scherl

Couté

Déon

et al. 2002

MBoC

445

378

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“…Moreover, these multiple stress factors can be integrated on the protein levels by the enzyme poly(ADPribose) polymerase (PARP). For a review see Tong et al (2001). This enzyme was demonstrated to be highly activated by both oxidative stress and chemotherapy treatment.…”

Section: Discussionmentioning

confidence: 99%

Temozolomide induces apoptosis and senescence in glioma cells cultured as multicellular spheroids

et al. 2003

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Temozolomide is an alkylating cytostatic drug that finds increasing application in the treatment of melanoma, anaplastic astrocytoma and glioblastoma multiforme. The compound is a prodrug that decomposes spontaneously, independent of an enzymatic activation step. DNA methylation induces futile mismatch repair cycles and depletion of the DNA repair enzyme O 6 -methylguanine-DNA methyltransferase should then initiate programmed cell death. We show drug-dependent inhibition of tumour growth in a threedimensional cell culture model of the glioma cell lines U87MG and GaMG. Migrational behaviour of the glioblastoma cells remained unaltered. However, coincubation of tumour spheroids with primary brain aggregates showed reduced tumour cell invasion into brain tissue in the presence of temozolomide. This was not achieved by slowing cellular migration, as temozolomide-treated cells displayed no reduced motility. By transferase-mediated dUTP nick-end labelling (TUNEL) of apoptotic nuclei, we found that the drug was able to induce apoptosis throughout the tumour cell spheroids. Apoptosis was highest in the core region of the spheroids. Repetitive application of sublethal doses of temozolomide to multicellular spheroids resulted in the development of drug resistance in GaMG cells. We suggest that temozolomide is a strong initiator of apoptosis in glioblastoma tumour cells in a spheroid cell culture system, when cells are already in a stressful environment.

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“…It appears to confer the majority of NAD þ -dependent PARP activity in cells. PARP-1 is activated in response to DNA damage and plays an important role in DNA repair processes, apoptosis, and cell cycle control (D'Amours et al, 1999;Burkle, 2001;Smith, 2001;Tong et al, 2001;Bouchard et al, 2003). PARP-2, PARP-3, Tankyrase-1 and -2, and VPARP are additional PARP enzymes that have been identified in recent years.…”

Section: Introductionmentioning

confidence: 99%