CDC20

PF3D7_1026400 (CDC20) is the single CDC20/CDH1 co-activator/adaptor homologue in Plasmodium and functions as an essential regulator of nuclear division during male gametogenesis while being dispensable for mitosis in asexual blood-stage schizogony (PMID:22383885, PMID:29618731). Deletion of the P. berghei orthologue arrests nuclear division at the spindle/kinetochore stage, blocking chromosome condensation and microgamete formation (PMID:22383885). Genome mining places CDC20 as the sole co-activator of a proposed minimal APC/C composed of APC3, APC10, APC11, and CDC20; consistent with a shared role in gametogenesis, loss of either CDC20 or APC3 causes failure of chromosome condensation and abnormal cytokinesis, though APC3 (unlike CDC20) is additionally required for schizogony (PMID:29618731). CDC20 undergoes stage-regulated phosphorylation that peaks in activated gametocytes and ookinetes, and its transcription rises in activated gametocytes in the absence of the sexual-development kinases MAP2 and CDPK4 (PMID:22383885). A direct physical interaction between CDC20 and the other APC/C subunits has not been demonstrated in the available corpus; membership in the minimal APC/C is inferred from comparative genomics and shared loss-of-function phenotypes (PMID:29618731).

1. 2012 High

   Whether the single Plasmodium CDC20/CDH1 homologue is required for cell division and at which life-cycle stage was unknown; targeted deletion resolved this by showing CDC20 is essential specifically for male gametogenesis but not for asexual mitosis.

   Evidence Gene deletion by double homologous recombination with DNA replication analysis, electron microscopy, and qRT-PCR in P. berghei

   PMID:22383885

   Open questions at the time

   • Molecular substrates of CDC20-directed degradation not identified
   • Direct physical partners not tested in this study
   • Mechanism restricting CDC20 essentiality to gametogenesis unresolved
2. 2012 Medium

   It was unclear whether CDC20 activity is post-translationally regulated across the life cycle; phosphorylation analysis showed stage-regulated modification peaking in activated gametocytes and ookinetes, linking CDC20 to the sexual developmental program.

   Evidence Phosphorylation analysis across parasite stages in P. berghei

   PMID:22383885

   Open questions at the time

   • Functional consequence of phosphorylation not directly tested
   • Responsible kinase(s) and phosphosites not defined
3. 2012 Medium

   The pathway relationship between CDC20 and the male-development kinases MAP2 and CDPK4 was unknown; transcriptional and phosphoproteomic analyses in kinase-deletion mutants indicated CDC20 acts downstream or in parallel and, versus MAP2, in an independent branch rather than a single linear pathway.

   Evidence qRT-PCR and global phosphoproteomic comparison in Δmap2 and Δcdpk4 mutant lines of P. berghei

   PMID:22383885

   Open questions at the time

   • Pathway placement inferred from transcript and global phosphorylation, not direct functional epistasis
   • No direct regulatory link between CDC20 and either kinase established
4. 2018 Medium

   Whether CDC20 operates within an APC/C-type machinery in Plasmodium was open; comparative genomics identified CDC20 as the sole APC/C co-activator and proposed a minimal APC/C (APC3, APC10, APC11, CDC20), with APC3 and CDC20 sharing a requirement in male gametogenesis.

   Evidence Comparative genomics plus reverse genetics of APC3 (disruption and conditional knockdown) with microscopy in P. berghei

   PMID:29618731

   Open questions at the time

   • Direct physical interaction of CDC20 with APC3/APC10/APC11 not demonstrated
   • Ubiquitination targets of the proposed complex unidentified
   • Reason for divergent APC3-vs-CDC20 requirement in schizogony unexplained

• The biochemical mechanism of CDC20 within the proposed minimal APC/C and its degradation substrates during gametogenesis remain undefined.
• No reconstitution or direct binding data for the CDC20-APC/C complex
• No identified substrates whose degradation drives chromosome condensation or cytokinesis
• Findings derive from P. berghei; role of PF3D7_1026400 in P. falciparum not directly characterized in the corpus