| APC1 serves as the largest scaffold subunit within the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase essential for mitotic progression and substrate-specific proteasomal degradation. Its architecture encompasses an N-terminal WD40 β-propeller domain linked via an α-helical solenoid to a central PC-repeat platform domain that anchors core APC/C components including APC4, APC5, and APC15, to form the structural platform. During prometaphase, CDK1 and PLK1 kinases target an N-terminal autoinhibitory loop in APC1 for multisite phosphorylation, inducing conformational release that exposes the coactivator-binding platform and permits CDC20 docking through direct interaction with APC1's WD40 repeats and APC8. This phospho-dependent switch allosterically rearranges the APC11-RING:APC2 catalytic module, enhancing recruitment of E2 enzymes UBE2C and UBE2S to initiate K11-linked polyubiquitination chains on D-box and KEN-box motifs of substrates like cyclin B, securin, and Aurora kinases. APC1 further stabilizes Cdh1 engagement in late mitosis and G1 via its extended platform interface, broadening substrate repertoire to include geminin and Cdt1 for licensing control. Mitotic phosphorylation peaks align with spindle assembly checkpoint satisfaction, with dephosphorylation by PP2A-B55δ enabling APC/C^Cdh1^ dominance for cytokinesis completion. The WD40 domain directly contacts CDC20's C-box, transmitting allosteric activation to the catalytic core while maintaining rotational flexibility for dynamic E2-substrate encounters. Ubiquitous expression supports universal applicability in cell cycle studies, with siRNA-mediated depletion yielding metaphase arrest and polyploidy. |
Lane 1: 293T, Lane 2: MOLT-4, Lane 3: MCF7, Lane 4: COS7
