Molecular recognition of the human coactivator CBP by the HIV-1 transcriptional activator Tat

被引:34
作者
Vendel, AC
Lumb, KJ [1 ]
机构
[1] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA
[2] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA
关键词
D O I
10.1021/bi0270034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
HIV-1 Tat is required for the expression of the viral genome. Tat binds to an RNA stem-loop and mediates the recruitment of human coactivators to facilitate HIV-1 transcription. The coactivator and acetyltransferase CREB binding protein (CBP), and the paralog p300, are recruited to the HIV-1 promoter by Tat. Here we identify the interacting domains of Tat and CBP. Circular dichroism and pulldown assays show that full-length Tat binds to the KIX domain of CBP, but not to the C/H1 or CR2 domains. Circular dichroism and NMR studies of Tat deletion mutants localize the KIX-binding domain of Tat to the N-terminal 24 residues of Tat. Transient cotransfections demonstrate that exogenous KIX behaves as a dominant negative to Tat-mediated transcription in human T-cells, suggesting that Tat and KIX interact in vivo. These findings indicate that Tat targets the KIX domain of CBP and provide insight into the molecular interactions involved in regulating HIV-1 gene expression.
引用
收藏
页码:910 / 916
页数:7
相关论文
共 41 条
[1]   STRUCTURAL STUDIES OF HIV-1 TAT PROTEIN [J].
BAYER, P ;
KRAFT, M ;
EJCHART, A ;
WESTENDORP, M ;
FRANK, R ;
ROSCH, P .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 247 (04) :529-535
[2]   Activation of integrated provirus requires histone acetyltransferase - p300 AND P/CAF are coactivators for HIV-1 Tat [J].
Benkirane, M ;
Chun, RF ;
Xiao, H ;
Ogryzko, VV ;
Howard, BH ;
Nakatani, Y ;
Jeang, KT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24898-24905
[3]   Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat [J].
Bieniasz, PD ;
Grdina, TA ;
Bogerd, HP ;
Cullen, BR .
EMBO JOURNAL, 1998, 17 (23) :7056-7065
[4]   Structurally distinct modes of recognition of the KIX domain of CBP by Jun and CREB [J].
Campbell, KM ;
Lumb, KJ .
BIOCHEMISTRY, 2002, 41 (47) :13956-13964
[5]  
Chan HM, 2001, J CELL SCI, V114, P2363
[6]   Tat-controlled protein acetylation [J].
Col, E ;
Gilquin, B ;
Caron, C ;
Khochbin, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (40) :37955-37960
[7]   Zinc-dependent protein folding [J].
Cox, EH ;
McLendon, GL .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (02) :162-165
[8]   Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals [J].
de la Fuente, Cynthia ;
Santiago, Francisco ;
Deng, Longwen ;
Eadie, Carolyne ;
Zilberman, Irene ;
Kehn, Kylene ;
Maddukuri, Anil ;
Baylor, Shanese ;
Wu, Kaili ;
Lee, Chee Gun ;
Pumfery, Anne ;
Kashanchi, Fatah .
BMC BIOCHEMISTRY, 2002, 3 :1-22
[9]   SPECTROSCOPIC DETERMINATION OF TRYPTOPHAN AND TYROSINE IN PROTEINS [J].
EDELHOCH, H .
BIOCHEMISTRY, 1967, 6 (07) :1948-&
[10]   CELLULAR UPTAKE OF THE TAT PROTEIN FROM HUMAN IMMUNODEFICIENCY VIRUS [J].
FRANKEL, AD ;
PABO, CO .
CELL, 1988, 55 (06) :1189-1193