Inhibition of cellular functions of HIV-1 Nef by artificial SH3 domains
| Autor: | G. Herma Renkema, Aki Manninen, Kalle Saksela, Marita Hiipakka, Päivi Huotari |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell signaling
NFAT animal structures HIV Infections macromolecular substances Biology Virus Replication environment and public health SH3 domain Gene Products nef Cell Line src Homology Domains Structure-Activity Relationship Virology Structure–activity relationship Humans nef Gene Products Human Immunodeficiency Virus Transcription factor Recombination Genetic Nef protein engineering Genetic Therapy gene therapy Cell biology SH3 RT-loop Cell culture PAK Cancer research HIV-1 Tyrosine kinase Intracellular |
| Zdroj: | Virology. 286(1) |
| ISSN: | 0042-6822 |
| Popis: | SH3 domains regulate many normal and pathological cellular processes by guiding specific protein interactions. Studies on binding of HIV-1 Nef to the SH3 domain of the Hck tyrosine kinase have indicated an important role for the SH3 RT-loop region in ligand binding. Here we have tested the potential of artificial Hck-derived SH3 domains carrying tailored RT-loops providing high affinity for Nef as intracellular inhibitors of Nef. These artificial SH3 domains efficiently associated with Nef in cells and thereby potently inhibited SH3-dependent Nef functions, such as association with p21-activated kinase-2 and induction of the transcription factor NFAT. On the other hand, biochemical and functional data indicated that the Nef-targeted SH3 domains were not prone to compete with normal SH3-mediated processes. Thus, RT-loop-modified SH3 domains represent a novel approach for selectively interfering with cellular signaling events, which could be exploited in research as well as in therapeutic applications. |
| Databáze: | OpenAIRE |
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