Practice question

CDK1-Cyclin B, historically termed Maturation Promoting Factor, orchestrates early mitotic transformations upon nuclear translocation. Its catalytic subunit CDK1 becomes competent after binding Cyclin B, phosphorylation at Thr161 by CAK and dephosphorylation of inhibitory Thr14/Tyr15 by Cdc25C. Once active, it phosphorylates serine-threonine-proline motifs on diverse substrates: lamins A-C at Ser22, Ser392 causing depolymerization of intermediate filament network and nuclear envelope breakdown, condensin subunits Cap-D2, Cap-H2 stimulating chromosome condensation, Golgi matrix proteins GRASP65, GM130 leading to fragmentation, nucleolar proteins B23 and fibrillarin releasing ribosome biogenesis components, and microtubule regulators Eg5 kinesin, TPX2, NuMA driving bipolar spindle assembly and centrosome separation. Global transcription inhibition and cap-dependent translation downregulation also result from phosphorylation of TFDII and 4E-BP1 relatives. DNA replication initiation, however, depends on distinct S-phase kinases CDK2-Cyclin E, Cyclin A plus DDK Cdc7-Dbf4 phosphorylating MCM2-7 and Cdc45 loader, a process actively suppressed during mitosis when CDK1-Cyclin B is high and replication licensing factors degraded, explaining why replication cannot be assigned to mitotic complex. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.