Characterization of a unique aspartate-rich protein of the SET/TAF-family in the human malaria parasite, Plasmodium falciparum, which inhibits protein phosphatase 2A
Abbreviated Journal Title
Mol. Biochem. Parasitol.
protein phosphatase; SET protein; Plasmodium falciparum; heat-stable; PP2A inhibitor; aspartate-rich protein; NF-KAPPA-B; OKADAIC ACID; CELL-PROLIFERATION; POTENT INHIBITOR; EXPRESSION; SET; GENE; IDENTIFICATION; ACTIVATION; TRANSCRIPTION; Biochemistry & Molecular Biology; Parasitology
A search for physiological inhibitors of protein phosphatases led to the identification of a Plasmodium falciparum (Pf) cDNA that had the potential to code for an aspartate-rich protein and hence named ARP. The PfARP was virtually identical to its Plasmodium berghei counterpart in gene structure and protein sequence. The PfARP coding sequence contained two introns, and the predicted protein contained 269 amino acid residues. Its primary structure showed significant similarity to eukaryotic proteins of the SET and TAF-family that included two inhibitors of mammalian serine/threonine protein phosphatase 2A (PP2A), namely I1(PP2A) and I2(PP2A). Like the SET and TAF proteins, it had an extremely acidic tail. The cDNA was confirmed by recombinant expression in bacteria. Native parasitic ARP was purified and was found to be highly thermostable. PfARP specifically inhibited the parasitic PP2A at nanomolar concentrations, with no effect on PP1, PP2B, PP5, or PPJ. Expression of PfARP in HeLa cells led to elevated phosphorylation of c-Jun, and activation of transcription factors AP1 and NF-kappa B. These functional properties are also characteristic of the SET/TAF-family proteins. The ARP mRNA and protein were detectable in all the erythrocytic asexual stages of the parasite, and the protein was located mainly in the parasitic cytoplasm. Thus, PfARP is a unique cytoplasmic member of the SET/TAF-family and a candidate physiological regulator of the Plasmodium PP2A. (C) 2003 Elsevier Science B.V. All rights reserved.
Molecular and Biochemical Parasitology
"Characterization of a unique aspartate-rich protein of the SET/TAF-family in the human malaria parasite, Plasmodium falciparum, which inhibits protein phosphatase 2A" (2003). Faculty Bibliography 2000s. 3703.