PfCullin-1 and PfCullin-2 serve as scaffolds for assembly of the indicated proteins into functional PfSCF (A) and PfCRL4 (B) ubiquitin E3 ligases, respectively. Both the complexes localize (C) to cytoplasm (Cyt) and nucleus (Nuc), and associate with chromatin (Chr), suggesting their roles in these compartments, including DNA-associated processes. Apicoplast (Ap), mitochondria (Mit) and food vacuole (FV) with haemozoin (black structure) are also shown in the parasite within the erythrocyte. PfCullin-2 knock-down at protein level would prevent assembly of the indicated subunits into functional PfCRL4 (D), thereby affecting the associated processes. Wild type asexual erythrocytic parasite developed normally from ring to multinucleate schizonts (E), whereas PfCullin-2 knock-down parasites exhibited down-regulation of several key pathways, resulting in a block in cell division and compromised membrane integrity (F). Contrary to the wild type schizont that showed multiple nuclei with distinct outer membrane and intracellular membraned structures, the PfCullin-2 knock-down schizont had less number of nuclei and poorly demarcated membraned structures. Rizvi Z, Reddy GS, Gorde SM, Pundir P, Das D, Sijwali PS. Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity. PLoS Pathog. 2024 28;20(2):e1012045. PMID: 38416790