Influence of human p16(INK4) and p21(CIP1) on the in vitro activity of recombinant Plasmodium falciparum cyclin-dependent protein kinases

The regulatory mechanisms of most cyclin dependent protein kinases (CDKs) a re well understood and are highly conserved in eukaryotes. CDKs from the ma laria parasite, Plasmodium falciparum, appear to be regulated in a similar manner with regard to cyclin binding and phosphorylation. In order to furth er understand their regulatory mechanisms, we examined two classes of cycli n dependent kinase inhibitors (CDIs) to inhibit a panel of plasmodial CDKs. We find that Pfmrk and PfPK5 are inhibited by heterologous p21(CIP1) with varying degrees of inhibition. In contrast, PfPK6, a kinase with sequence f eatures characteristic of both a CDK and MAP kinase, is unaffected by this CDI. Furthermore, the CDK4/6 specific CDI, p16(INK4), fails to inhibit thes e plasmodial CDKs. Taken together, these results suggest that plasmodial CD Ks may be regulated by the binding of inhibitory proteins in vivo. (C) 2001 Academic Press.