Interaction of HIV-1 Integrase with DNA Repair Protein hRad18
| Autor: | Mark A. Muesing, Lubbertus C. F. Mulder, Lisa A. Chakrabarti |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
DNA Repair
DNA repair Ubiquitin-Protein Ligases Blotting Western HIV Integrase Protein degradation Transfection Biochemistry Cell Line DNA Repair Protein Humans Molecular Biology chemistry.chemical_classification Genetics biology Cell Biology DNA Repair Pathway Precipitin Tests Protein Structure Tertiary Cell biology Integrase Ubiquitin ligase DNA-Binding Proteins RING finger domain Retroviridae Enzyme Microscopy Fluorescence chemistry Mutation biology.protein Gene Deletion Plasmids Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 277:27489-27493 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m203061200 |
| Popis: | We have previously shown that human immunodeficiency virus-1 (HIV-1) integrase is an unstable protein and a substrate for the N-end rule degradation pathway. This degradation pathway shares its ubiquitin-conjugating enzyme, Rad6, with the post-replication/translesion DNA repair pathway. Because DNA repair is thought to play an essential role in HIV-1 integration, we investigated whether other molecules of this DNA repair pathway could interact with integrase. We observed that co-expression of human Rad18 induced the accumulation of an otherwise unstable form of HIV-1 integrase. This accumulation occurred even though hRAD18 possesses a RING finger domain, a structure that is generally associated with E3 ubiquitin ligase function and protein degradation. Evidence for an interaction between integrase and hRad18 was obtained through reciprocal co-immunoprecipitation. Moreover we found that a 162-residue region of hRad18 (amino acids 65-226) was sufficient for both integrase stabilization and interaction. Finally, we observed that HIV-1 integrase co-localized with hRad18 in nuclear structures in a subpopulation of co-transfected cells. Taken together, these findings identify hRad18 as a novel interacting partner of HIV-1 integrase and suggest a role for post-replication/translesion DNA repair in the retroviral integration process. |
| Databáze: | OpenAIRE |
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