Evidence map›Paper›PMID 21510906›Full record

ArticleRetrovirology2011

HIV-1 integrase modulates the interaction of the HIV-1 cellular cofactor LEDGF/p75 with chromatin.

Paulina Astiazaran, Murilo Td Bueno, Elisa Morales, Jeffrey R Kugelman, Jose A Garcia-Rivera, Manuel Llano

Abstract read
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Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Paulina AstiazaranDepartment of Biological Sciences, University of Texas at El Paso, 500 West University Ave, El Paso, TX 79968, USA.
Murilo Td Bueno
Elisa Morales
Jeffrey R Kugelman
Jose A Garcia-Rivera
Manuel Llano

Funding

TOXICOLOGY PROJECTG12RR008124 · NCRR · UNIVERSITY OF TEXAS EL PASO · PI WALSH, ELIZABETH J · 1992 to 2011
$20.8M
RISE Scholars Program at UTEPR25GM069621 · NIGMS · UNIVERSITY OF TEXAS EL PASO · PI AGUILERA, RENATO J · 2004 to 2021
$11.2M
Molecular Mechanism of LEDGF/p75 in HIV IntegrationSC2GM082301 · NIGMS · UNIVERSITY OF TEXAS EL PASO · PI LLANO, MANUEL · 2008 to 2010
$407k
NCRR NIH HHS 5G12RR008124NIGMS NIH HHS 1SC2GM082301-01NIGMS NIH HHS 2R25GM069621-05
6 · The paper itself

Abstract

backgroundChromatin binding plays a central role in the molecular mechanism of LEDGF/p75 in HIV-1 DNA integration. Conflicting results have been reported in regards to the relevance of the LEDGF/p75 chromatin binding element PWWP domain in its HIV-1 cofactor activity.

resultsHere we present evidence that re-expression of a LEDGF/p75 mutant lacking the PWWP domain (ΔPWWP) rescued HIV-1 infection in cells verified to express background levels of endogenous LEDGF/p75 that do not support efficient HIV-1 infection. The HIV-1 cofactor activity of LEDGF/p75 ΔPWWP was similar to that of LEDGF/p75 wild type (WT). A possible molecular explanation for the nonessential role of PWWP domain in the HIV-1 cofactor activity of LEDGF/p75 comes from the fact that coexpression of HIV-1 integrase significantly restored the impaired chromatin binding activity of LEDGF/p75 ΔPWWP. However, integrase failed to promote chromatin binding of a non-chromatin bound LEDGF/p75 mutant that lacks both the PWWP domain and the AT hook motifs (ΔPWWP/AT) and that exhibits negligible HIV-1 cofactor activity. The effect of integrase on the chromatin binding of LEDGF/p75 requires the direct interaction of these two proteins. An HIV-1 integrase mutant, unable to interact with LEDGF/p75, failed to enhance chromatin binding, whereas integrase wild type did not increase the chromatin binding strength of a LEDGF/p75 mutant lacking the integrase binding domain (ΔIBD).

conclusionsOur data reveal that the PWWP domain of LEDGF/p75 is not essential for its HIV-1 cofactor activity, possibly due to an integrase-mediated increase of the chromatin binding strength of this LEDGF/p75 mutant.

Indexed as

Protein Interaction MappingVirus IntegrationCell LineChromatinHIV-1HIV IntegraseHumansIntercellular Signaling Peptides and ProteinsMutant ProteinsProtein BindingProtein Interaction Domains and MotifsSequence DeletionChromatinHIV IntegraseIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorMutant Proteinsp31 integrase protein, Human immunodeficiency virus 1

Identifiers

PMID21510906
PMCPMC3098157

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.