scholarly journals Identification of an Evolutionarily Conserved Domain in Human Lens Epithelium-derived Growth Factor/Transcriptional Co-activator p75 (LEDGF/p75) That Binds HIV-1 Integrase

2004 ◽  
Vol 279 (47) ◽  
pp. 48883-48892 ◽  
Author(s):  
Peter Cherepanov ◽  
Eric Devroe ◽  
Pamela A. Silver ◽  
Alan Engelman
2009 ◽  
Vol 84 (2) ◽  
pp. 740-752 ◽  
Author(s):  
Jose A. Garcia-Rivera ◽  
Murilo T. D. Bueno ◽  
Elisa Morales ◽  
Jeffrey R. Kugelman ◽  
Daniel F. Rodriguez ◽  
...  

ABSTRACT Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular cofactor for HIV-1 DNA integration. It is well established that the simultaneous binding of LEDGF/p75 to chromatin and to HIV-1 integrase is required for its cofactor activity. However, the exact molecular mechanism of LEDGF/p75 in HIV-1 integration is not yet completely understood. Our hypothesis is that evolutionarily conserved regions in LEDGF/p75 exposed to solvent and harboring posttranslational modifications may be involved in its HIV-1 cofactor activity. Therefore, a panel of LEDGF/p75 deletion mutants targeting these protein regions were evaluated for their HIV-1 cofactor activity, chromatin binding, integrase interaction, and integrase-to-chromatin-tethering activity by using different cellular and biochemical approaches. The deletion of amino acids 267 to 281 reduced the cofactor activity of LEDGF/p75 to levels observed for chromatin-binding-defective mutants. This region contains a serine cluster (residues 271, 273, and 275) recurrently found to be phosphorylated in both human and mouse cells. Importantly, the conversion of these Ser residues to Ala was sufficient to impair the ability of LEDGF/p75 to mediate HIV-1 DNA integration, although these mutations did not alter chromatin binding, integrase binding, or the integrase-to-chromatin-tethering capability of LEDGF/p75. These results clearly indicated that serine residues 271, 273, and 275 influence the HIV-1 cofactor activity of integrase-to-chromatin-tethering-competent LEDGF/p75.


2016 ◽  
Vol 57 (10) ◽  
pp. 4063 ◽  
Author(s):  
Rosana Mesa ◽  
Manoj Tyagi ◽  
George Harocopos ◽  
David Vollman ◽  
Steven Bassnett

2010 ◽  
Vol 107 (7) ◽  
pp. 3135-3140 ◽  
Author(s):  
A. L. Ferris ◽  
X. Wu ◽  
C. M. Hughes ◽  
C. Stewart ◽  
S. J. Smith ◽  
...  

1990 ◽  
Vol 2 (1) ◽  
pp. 71-73 ◽  
Author(s):  
Margaret J. Jeffrey ◽  
W.T. Green ◽  
D.L. Boase ◽  
M.N. Jeffrey

RSC Advances ◽  
2019 ◽  
Vol 9 (29) ◽  
pp. 16596-16605 ◽  
Author(s):  
Belal I. Hanafy ◽  
Gareth W. V. Cave ◽  
Yvonne Barnett ◽  
Barbara Pierscionek

Nanoceria (<5 nm), stabilised with ethylene glycol, protects human lens epithelium from oxidative stress and exhibits multicoloured photoluminescence.


2004 ◽  
Vol 279 (53) ◽  
pp. 55570-55577 ◽  
Author(s):  
Manuel Llano ◽  
Sharon Delgado ◽  
Maria Vanegas ◽  
Eric M. Poeschla

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