CYC4

CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins identified in silico from the genome, with the corresponding polypeptides expressed in erythrocytic blood stages (PMID:12869562). Within this set of three cyclins, at least one member associates with histone H1 kinase activity in parasite extracts and activates the CDK homologue PfPK5 in vitro, demonstrating cyclin activity for the group; however, the available corpus does not individually resolve which of these activities apply to CYC4 specifically (PMID:12869562). Beyond its membership in this set of novel cyclins and its erythrocytic-stage expression (PMID:12869562), no experiment has individually and mechanistically characterized CYC4 in the available corpus.

1. 2003 Low

   Before this work it was unknown whether P. falciparum encodes cyclin-type regulators for its CDK homologues; the identification of three novel cyclins expressed in blood stages and showing cyclin activity established that such regulators exist and are active during the erythrocytic cycle.

   Evidence In silico identification from genome sequence, Western blot/immunoprecipitation for erythrocytic-stage expression, histone H1 kinase co-immunoprecipitation from parasite extracts, and in vitro PfPK5 activation assay with recombinant protein

   PMID:12869562

   Open questions at the time

   • The abstract does not resolve whether the histone H1 kinase association or PfPK5 activation is attributable to CYC4 specifically versus the other two novel cyclins
   • No CYC4-specific binding partner, substrate, or in vivo function has been demonstrated
   • No subcellular localization or structural characterization of CYC4 is provided

• It remains unknown which specific CDK partner CYC4 activates, what its substrates are, and what role it plays in the parasite cell cycle independent of the other two novel cyclins.
• No experiment individually characterizes CYC4 apart from the group of three cyclins
• No genetic or knockdown phenotype for CYC4 has been reported
• The CDK partnership and substrate specificity of CYC4 itself are undefined