Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vaults are ribonucleoproteins of unknown function, consisting of three different proteins and multiple copies of small untranslated RNA molecules. One of the protein subunits has been identified as TEP1, a protein that is also associated with the telomerase complex. Another protein appears to contain a functional PARP domain and is hence called VPARP. The third protein, major vault protein (MVP), is believed to make up 70% of the total mass of the vault complex and to be responsible for the typical barrel-shaped structure of vaults. We have isolated the murine MVP cDNA and compared the amino acid sequence with MVP from other species. Over 90% of sequence identity was found between mouse, human and rat, and a considerable degree of identity between mouse and MVPs from lower eukaryotes. We also found that the genomic structure of the murine MVP gene closely resembles the organization of the human MVP gene, both consisting of 15 exons of which most have exactly the same size. Finally we have isolated a genomic region upstream (and partially overlapping) the first untranslated exon, that displayed promoter activity in a luciferase reporter assay. Furthermore, we showed that the sequences from the first exon together with the 5'-end of the first intron enhance the promoter activity, implying the presence of essential promoter elements in this region. Alignment of the murine promoter region with the homologous sequences of the human gene revealed an identity of 58%. The apparent presence of conserved promoter elements suggests a similar regulation of human and murine MVP expression.
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PMID:The genomic sequence of the murine major vault protein and its promoter. 1223 84

To test the role of poly(ADP-ribose) polymerase on the telomerase activity, we determined the telomerase activity in leukemic cells K562 treated with benzamide and 4-amino 1,8 naphthalimide (NAP), the inhibitors of PARP. We observed that both the agents inhibited telomerase activity in a dose-dependent manner. The doses of benzamide and NAP that inhibited telomerase activity to 50% of untreated control cells were 10.7 +/- 0.6 mm and 200 +/- 7 microm, respectively. Benzamide treatment (10 mm) inhibited telomerase activity in a time-dependent manner. We also tested the ability of benzamide to inhibit the telomerase activity in Chinese hamster V79 cells and observed similar inhibition of the telomerase activity. Expression of telomerase reverse transcriptase (TERT) and telomerase RNA component, detected by RT-PCR, remained unaltered by treatment with benzamide or NAP. On the contrary, the expression of telomerase associated protein (TEP1/TP1), as detected by RT-PCR and western blot analysis, was reduced by both the agents. Further, in K562 cells, immunoprecipitation with the anti-TERT IgG and probed anti-poly (ADP-ribose) IgG revealed that TERT was poly(ADP-ribosyl)ated in the physiological condition of cell growth and such poly(ADP-ribosyl)ation was inhibited by benzamide treatment. Decrease in TEP1/TP1 expression and poly(ADP-ribosyl)ation of TERT were correlated with the inhibition of PARP activity by benzamide, indicating that PARP had a role in telomerase activity through poly(ADP-ribosyl)ation of TERT and down-regulation of TEP1/TP1.
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PMID:Benzamide and 4-amino 1,8 naphthalimide treatment inhibit telomerase activity by down-regulating the expression of telomerase associated protein and inhibiting the poly(ADP-ribosyl)ation of telomerase reverse transcriptase in cultured cells. 1609 4

Inhibitors of poly(ADP-ribose) polymerase (PARP) have been shown to reduce the telomerase activity in cultured cells. To find out the specific member of the PARP family, which participates in the regulation of telomerase activity, in the present investigation, we knocked down the PARP-1 gene by siRNA in HeLa cells and studied the telomerase activity. Reduction of expression of PARP-1 by siRNA increased cellular NAD(+) level and decreased general poly(ADP-ribosyl)ation of proteins. Telomerase activity decreased in cells with knocked down PARP-1 gene. Besides, we observed that telomerase reverse transcriptase (hTERT) was poly(ADP-ribosyl)ated in HeLa cells and such modification was decreased in cells with reduced PARP-1 expression. In addition, the expression of telomerase-associated protein 1 (TEP1/TP1) subunit of human telomerase holoenzyme reduced significantly in PARP-1 knock down HeLa cells. Thus, PARP-1 modulates the telomerase activity by altering poly(ADP-ribosyl)ation of TERT and/or the expression of TEP1/TP1.
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PMID:Inhibition of telomerase activity by reduction of poly(ADP-ribosyl)ation of TERT and TEP1/TP1 expression in HeLa cells with knocked down poly(ADP-ribose) polymerase-1 (PARP-1) gene. 1714 Dec 79