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

被引：13

作者：

Ghosh, Utpal

Das, Nilanjana

Bhattacharyya, Nitai P.

机构：

[1] Saha Inst Nucl Phys, Crystallog & Mol Biol Div, Kolkata 700064, W Bengal, India

[2] Univ Kalyani, Dept Biochem & Biophys, Kalyani 741235, W Bengal, India

来源：

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS | 2007年 / 615卷 / 1-2期

关键词：

poly(ADP-ribosyl)ation; PARP; PAR; TERT; TEP1/TP1; siRNA; HeLa; NAD(+); telomerase;

D O I：

10.1016/j.mrfmmm.2006.10.002

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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. (c) 2006 Elsevier B.V. All rights reserved.

引用

页码：66 / 74

页数：9

共 28 条

[1] The PARP superfamily
Amé, JC
Spenlehauer, C
de Murcia, G
[J]. BIOESSAYS, 2004, 26 (08) : 882 - 893
[2] TERT regulates cell survival independent of telomerase enzymatic activity
Cao, Y
Li, H
Deb, S
Liu, JP
[J]. ONCOGENE, 2002, 21 (20) : 3130 - 3138
[3] Differential gene expression in γ-irradiated BALB/3T3 fibroblasts under the influence of 3-aminobenzamide, an inhibitior of parp enzyme
Cardoso, RS
Espanhol, AR
Passos, GAS
Sakamoto-Hojo, ET
[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2002, 508 (1-2) : 33 - 40
[4] Differential regulation of telomerase activity by six telomerase subunits
Chang, JTC
Chen, YL
Yang, HT
Chen, CY
Cheng, AJ
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (14): : 3442 - 3450
[5] Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions
D'Amours, D
Desnoyers, S
D'Silva, I
Poirier, GG
[J]. BIOCHEMICAL JOURNAL, 1999, 342 : 249 - 268
[6] Functional interaction between poly(ADP-ribose) polymerase 2 (PARP-2) and TRF2:: PARP activity negatively regulates TRF2
Dantzer, F
Giraud-Panis, MJ
Jaco, I
Amé, JC
Schultz, I
Blasco, M
Koering, CE
Gilson, E
Ménissier-de Murcia, J
de Murcia, G
Schreiber, V
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (04) : 1595 - 1607
[7] Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse
de Murcia, JMN
Ricoul, M
Tartier, L
Niedergang, C
Huber, A
Dantzer, F
Schreiber, V
Amé, JC
Dierich, A
LeMeur, M
Sabatier, L
Chambon, P
de Murcia, G
[J]. EMBO JOURNAL, 2003, 22 (09) : 2255 - 2263
[8] di Fagagna FD, 1999, NAT GENET, V23, P76
[9] Specific interference with gene expression and gene function mediated by long dsRNA in neural cells
Gan, L
Anton, KE
Masterson, BA
Vincent, VAM
Ye, S
Gonzalez-Zulueta, M
[J]. JOURNAL OF NEUROSCIENCE METHODS, 2002, 121 (02) : 151 - 157
[10] 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
Ghosh, U
Bhattacharyya, NP
[J]. FEBS JOURNAL, 2005, 272 (16) : 4237 - 4248

← 1 2 3 →