Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, INTEGRASE-BINDING DOMAIN, HIV-1 INTEGRASE, NUP98-LEDGF FUSION, COMPLEX-FORMATION, LEDGF/P75, PROTEIN, IDENTIFICATION, NUCLEAR, GENE, RECOGNITION, Amino Acid Sequence, Binding, Competitive, Cell Line, Tumor, HIV Integrase, HeLa Cells, Humans, Intercellular Signaling Peptides and Proteins, Lentivirus, Models, Biological, Molecular Sequence Data, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid, Transposases, Two-Hybrid System Techniques, Hela Cells, 03 Chemical Sciences, 06 Biological Sciences, 11 Medical and Health Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 34 Chemical sciences

Abstract:

Lens epithelium-derived growth factor/p75 (LEDGF/p75) is a prominent cellular interaction partner of human immunodeficiency virus-1 (HIV-1) integrase, tethering the preintegration complex to the host chromosome. In light of the development of LEDGF/p75-integrase interaction inhibitors, it is essential to understand the cell biology of LEDGF/p75. We identified pogZ as new cellular interaction partner of LEDGF/p75. Analogous to lentiviral integrase, pogZ, a domesticated transposase, carries a DDE domain, the major determinant for LEDGF/p75 interaction. Using different in vitro and in vivo approaches, we corroborated the interaction between the C terminus of LEDGF/p75 and the DDE domain of pogZ, revealing an overlap in the binding of pogZ and HIV-1 integrase. Competition experiments showed that integrase is efficient in displacing pogZ from LEDGF/p75. Moreover, pogZ does not seem to play a role as a restriction factor of HIV. The finding that LEDGF/p75 is capable of interacting with a DDE domain protein that is not a lentiviral integrase points to a profound role of LEDGF/p75 in DDE domain protein function.