Ramya, T. N. C. ; Karmodiya, Krishanpal ; Surolia, Avadhesha ; Surolia, Namita (2007) 15-Deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum Journal of Biological Chemistry, 282 (9). pp. 6388-6397. ISSN 0021-9258
Full text not available from this repository.
Official URL: http://www.jbc.org/content/282/9/6388.short
Related URL: http://dx.doi.org/10.1074/jbc.M610251200
Abstract
15-Deoxyspergualin, an immunosuppressant with tumoricidal and antimalarial properties, has been implicated in the inhibition of a diverse array of cellular processes including polyamine synthesis and protein synthesis. Endeavoring to identify the mechanism of antimalarial action of this molecule, we examined its effect on Plasmodium falciparum protein synthesis, polyamine biosynthesis, and transport. 15-Deoxyspergualin stalled protein synthesis in P. falciparum through Hsp70 sequestration and subsequent phosphorylation of the eukaryotic initiation factor eIF2α. However, protein synthesis inhibition as well as polyamine depletion were invoked only by high micromolar concentrations of 15-deoxyspergualin, in contrast to the submicromolar concentrations sufficient to inhibit parasite growth. Further investigations demonstrated that 15-deoxyspergualin in the malaria parasite primarily targets the hitherto underexplored process of trafficking of nucleus-encoded proteins to the apicoplast. Our finding that 15-deoxyspergualin kills the malaria parasite by interfering with targeting of nucleus-encoded proteins to the apicoplast not only exposes a chink in the armor of the malaria parasite, but also reveals new realms in our endeavors to study this intriguing biological process.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology. |
ID Code: | 55354 |
Deposited On: | 18 Aug 2011 12:09 |
Last Modified: | 03 Oct 2011 14:09 |
Repository Staff Only: item control page