PIAS3 modulate HIV-1 integrase SUMOylation

Abstract

Background HIV-1 hijacks cellular machineries to replicate. Posttranslational modifications, like acetylation, phosphorylation or ubiquitination are not exception. We are interested in studying the interplay between HIV-1 and the SUMOylation pathway. SUMOylation consists in the covalent attachment of SUMO (Small Ubiquitin-like Modifier) proteins to a lysine residue of a target protein, often found within a consensus motif (ΨKxD/E, where Ψ is a hydrophobic residue, x is any amino acid, D or E is an acidic residue). SUMO proteins share structural similarities with ubiquitin, and are conjugated to the substrate by an analogous but distinct enzymatic cascade requiring the sequential action of E1 activating enzyme (SAE1/SAE2 heterodimer), E2 conjugating enzyme (Ubc9), and E3 ligases. So far, several E3 SUMO ligases have been characterized, such as nuclear pore complex component Ran-binding protein 2 (RanBP2), protein-inhibitor of activated STAT (PIAS) family proteins, etc. Despite that Ubc9 can directly transfer SUMO moieties to acceptor lysine residues, E3 SUMO ligases promote specificity and/or efficiency of SUMO conjugation. We have recently shown that HIV-1 integrase, the viral enzyme that is responsible for viral genome integration into host cellular chromosome, is SUMOylated. Virions harboring a SUMOylation-defective integrase are less infectious than WT HIV-1, indicating that this modification is important for efficient viral replication [1].