Cyclin CYC3 (CYC3)

Cyclin CYC3 is a regulatory protein in the protozoan parasite Leishmania donovani, the causative agent of visceral leishmaniasis (Gour et al., 2012). It belongs to the P-type cyclin family and serves as the essential activating partner for the Cdc2-related kinase 3 (CRK3), which is the leishmanial ortholog of the human CDK1 kinase (Hammarton et al., 2003). The CRK3-CYC3 complex plays a pivotal role in the parasite's cell cycle, specifically governing the transition from the G2 phase to mitosis (UniProt E9BTM6). Because this complex is vital for the replication of both the insect-stage promastigotes and the mammalian-stage amastigotes, it is a major focus for antileishmanial drug discovery (Gour et al., 2012). Inhibition of the CRK3-CYC3 complex by small molecules like flavopiridol or roscovitine leads to irreversible cell cycle arrest and parasite death (Hammarton et al., 2003). Current research aims to develop small-molecule inhibitors that selectively target the parasite complex over human cyclin-dependent kinases to ensure safety and efficacy in treating leishmaniasis (Gour et al., 2012).

Other names

P-type cyclin CYC3Cyc3LdCYC3Cyclin-dependent kinase regulatory subunit CYC3CRK3-activating cyclin

Inhibition of the CRK3-CYC3 complex activity, which prevents the phosphorylation of downstream substrates required for the G2/M transition, resulting in cell cycle arrest and parasite death (Hammarton et al., 2003; Gour et al., 2012).