RNA interference directed to CDK2 inhibits HIV-1 transcription

被引：32

作者：

Ammosova, T

Berro, R

Kashanchi, F

Nekhai, S

机构：

[1] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA

[2] Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC 20059 USA

[3] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA

来源：

VIROLOGY | 2005年 / 341卷 / 02期

关键词：

HIV-1; CDK2; transcription; RNA interference; Tat;

D O I：

10.1016/j.virol.2005.06.041

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In the present study, CDK2-specific RNA interference in cultured HEK293T cells inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells and potently blocked TNF alpha-induced HIV-1 viral replication in OM 10.1 cells. CDK2-specific RNA interference did not have an effect on cell cycle progression, but it augmented TNF alpha-induced apoptosis of OM 10.1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：171 / 178

页数：8

共 15 条

[1] Antiviral activity of CYC202 in HIV-1-infected cells
Agbottah, E
de la Fuente, C
Nekhai, S
Barnett, A
Gianella-Borradori, A
Pumfery, A
Kashanchi, F
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (04) : 3029 - 3042
[2] Nuclear protein phosphatase-1 regulates HIV-1 transcription
Ammosova, T
Jerebtsova, M
Beullens, M
Voloshin, Y
Ray, PE
Kumar, A
Bollen, M
Nekhai, S
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) : 32189 - 32194
[3] Cdk2 knockout mice are viable
Berthet, C
Aleem, E
Coppola, V
Tessarollo, L
Kaldis, P
[J]. CURRENT BIOLOGY, 2003, 13 (20) : 1775 - 1785
[4] Loss of G1/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1
Clark, E
Santiago, F
Deng, LW
Chong, SY
de la Fuente, C
Wang, L
Fu, P
Stein, D
Denny, T
Lanka, V
Mozafari, F
Okamoto, T
Kashanchi, F
[J]. JOURNAL OF VIROLOGY, 2000, 74 (11) : 5040 - 5052
[5] HIV-1 tat interaction with RNA polymerase IIC-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter
Deng, LW
Ammosova, T
Pumfery, A
Kashanchi, F
Nekhai, S
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (37) : 33922 - 33929
[6] Cell cycle-regulated transcription by the human immunodeficiency virus type 1 Tat transactivator
Kashanchi, F
Agbottah, ET
Pise-Masison, CA
Mahieux, R
Duvall, J
Kumar, A
Brady, JN
[J]. JOURNAL OF VIROLOGY, 2000, 74 (02) : 652 - 660
[7] DETECTION OF REPLICATION-COMPETENT AND PSEUDOTYPED HUMAN-IMMUNODEFICIENCY-VIRUS WITH A SENSITIVE CELL-LINE ON THE BASIS OF ACTIVATION OF AN INTEGRATED BETA-GALACTOSIDASE GENE
KIMPTON, J
EMERMAN, M
[J]. JOURNAL OF VIROLOGY, 1992, 66 (04) : 2232 - 2239
[8] Malumbres M, 2003, ADV EXP MED BIOL, V532, P1
[9] A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity
Nekhai, S
Shukla, RR
Kumar, A
[J]. JOURNAL OF VIROLOGY, 1997, 71 (10) : 7436 - 7441
[10] Cell cycle-dependent stimulation of the HIV-1 promoter by Tat-associated CAK activator
Nekhai, S
Shukla, RR
Fernandez, A
Kumar, A
Lamb, NJC
[J]. VIROLOGY, 2000, 266 (02) : 246 - 256

← 1 2 →