Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZ.
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.
Bartholomeeusen
Koen
K
Laboratory for Molecular Virology and Gene Therapy, Division of Molecular Medicine, Katholieke Universiteit Leuven, Kapucijnenvoer 33, Flanders, Belgium.
Christ
Frauke
F
Hendrix
Jelle
J
Rain
Jean-Christophe
JC
Emiliani
Stéphane
S
Benarous
Richard
R
Debyser
Zeger
Z
Gijsbers
Rik
R
De Rijck
Jan
J
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D019427:HIV Integrase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D019895:Transposases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D020798:Two-Hybrid System Techniques; D004268:DNA-Binding Proteins; D018797:Cell Cycle Proteins
D019427:HIV Integrase; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D019895:Transposases; C541037:POGZ protein, human; D004268:DNA-Binding Proteins; D018797:Cell Cycle Proteins; C119380:lens epithelium-derived growth factor; C514801:p31 integrase protein, Human immunodeficiency virus 1