A role for LEDGF/p75 in targeting HIV DNA integration

被引：500

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

页码：1287 / 1289

页数：3

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
Cherepanov, P
Devroe, E
Silver, PA
Engelman, A
[J]. 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
Cherepanov, P
Maertens, G
Proost, P
Devreese, B
Van Beeumen, J
Engelborghs, Y
De Clercq, E
Debyser, Z
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (01) : 372 - 381
[4] Retrovirus-delivered siRNA
Devroe E.
Silver P.A.
[J]. BMC Biotechnology, 2 (1)
[5] Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation
Ge, H
Si, YZ
Roeder, RG
[J]. EMBO JOURNAL, 1998, 17 (22) : 6723 - 6729
[6] Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription
Lewinski, MK
Bisgrove, D
Shinn, P
Chen, H
Hoffmann, C
Hannenhalli, S
Verdin, E
Berry, CC
Ecker, JR
Bushman, FD
[J]. JOURNAL OF VIROLOGY, 2005, 79 (11) : 6610 - 6619
[7] Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase
Llano, M
Delgado, S
Vanegas, M
Poeschla, EM
[J]. 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
Llano, M
Vanegas, M
Fregoso, O
Saenz, D
Chung, S
Peretz, M
Poeschla, EM
[J]. 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
Maertens, G
Cherepanov, P
Pluymers, W
Busschots, K
De Clercq, E
Debyser, Z
Engelborghs, Y
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) : 33528 - 33539
[10] Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences
Mitchell, RS
Beitzel, BF
Schroder, ARW
Shinn, P
Chen, HM
Berry, CC
Ecker, JR
Bushman, FD
[J]. PLOS BIOLOGY, 2004, 2 (08) : 1127 - 1137

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