Acetylation of HIV-1 Integrase by P300 Regulates Viral Integration

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2005 Aug 13

PMID 16096645

Citations 86

Authors

Anna Cereseto

Lara Manganaro

Maria Ines Gutierrez

Mariaelena Terreni

Antonio Fittipaldi

Marina Lusic

Alessandro Marcello

Mauro Giacca

Affiliations

Soon will be listed here.

Abstract

Integration of HIV-1 into the human genome, which is catalyzed by the viral protein integrase (IN), preferentially occurs near transcriptionally active genes. Here we show that p300, a cellular acetyltransferase that regulates chromatin conformation through the acetylation of histones, also acetylates IN and controls its activity. We have found that p300 directly binds IN both in vitro and in the cells, as also specifically demonstrated by fluorescence resonance energy transfer technique analysis. This interaction results in the acetylation of three specific lysines (K264, K266, K273) in the carboxy-terminus of IN, a region that is required for DNA binding. Acetylation increases IN affinity to DNA, and promotes the DNA strand transfer activity of the protein. In the context of the viral replication cycle, point mutations in the IN acetylation sites abolish virus replication by specifically impairing its integration capacity. This is the first demonstration that HIV-1 IN activity is specifically regulated by post-translational modification.

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