A role for LEDGF/p75 in targeting HIV DNA integration

被引：499

作者：

Ciuffi, A

Llano, M

Poeschla, E

Hoffmann, C

Leipzig, J

Shinn, P

Ecker, JR

Bushman, F

机构：

[1] Mayo Clin & Mayo Fdn, Coll Med, Program Mol Med, Rochester, MN 55905 USA

[2] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[3] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA

来源：

NATURE MEDICINE | 2005年 / 11卷 / 12期

关键词：

D O I：

10.1038/nm1329

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 DNA integration is favored in active genes, but the underlying mechanism is unclear. Cellular lens epithelium-derived growth factor (LEDGF/p75) binds both chromosomal DNA and HIV integrase, and might therefore direct integration by a tethering interaction. We analyzed HIV integration in cells depleted for LEDGF/p75, and found that integration was (i) less frequent in transcription units, (ii) less frequent in genes regulated by LEDGF/p75 and (iii) more frequent in GC-rich DNA. LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells.

引用

收藏

页码：1287 / 1289

页数：3

相关论文

共 16 条

[1]

BUSHMAN F, 2005, NAT REV MICRO

[2] Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase [J].

Cherepanov, P ;

Devroe, E ;

Silver, PA ;

Engelman, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (47) :48883-48892

[3] HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells [J].

Cherepanov, P ;

Maertens, G ;

Proost, P ;

Devreese, B ;

Van Beeumen, J ;

Engelborghs, Y ;

De Clercq, E ;

Debyser, Z .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (01) :372-381

[4] Retrovirus-delivered siRNA [J].

Devroe E. ;

Silver P.A. .

BMC Biotechnology, 2 (1)

[5] Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation [J].

Ge, H ;

Si, YZ ;

Roeder, RG .

EMBO JOURNAL, 1998, 17 (22) :6723-6729

[6] Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription [J].

Lewinski, MK ;

Bisgrove, D ;

Shinn, P ;

Chen, H ;

Hoffmann, C ;

Hannenhalli, S ;

Verdin, E ;

Berry, CC ;

Ecker, JR ;

Bushman, FD .

JOURNAL OF VIROLOGY, 2005, 79 (11) :6610-6619

[7] Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase [J].

Llano, M ;

Delgado, S ;

Vanegas, M ;

Poeschla, EM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (53) :55570-55577

[8] LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes [J].

Llano, M ;

Vanegas, M ;

Fregoso, O ;

Saenz, D ;

Chung, S ;

Peretz, M ;

Poeschla, EM .

JOURNAL OF VIROLOGY, 2004, 78 (17) :9524-9537

[9] LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells [J].

Maertens, G ;

Cherepanov, P ;

Pluymers, W ;

Busschots, K ;

De Clercq, E ;

Debyser, Z ;

Engelborghs, Y .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) :33528-33539

[10] Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences [J].

Mitchell, RS ;

Beitzel, BF ;

Schroder, ARW ;

Shinn, P ;

Chen, HM ;

Berry, CC ;

Ecker, JR ;

Bushman, FD .

PLOS BIOLOGY, 2004, 2 (08) :1127-1137