Practice question

Spindle construction requires cooperation between CDK1 and two mitotic kinase families distinct from CDKs. Aurora kinases A, B, C share conserved catalytic domains but differ in localization. Aurora A at centrosomes phosphorylates TACC3, ch-TOG, LATS2, CEP192 increasing pericentriolar material recruitment and microtubule nucleation. Aurora B as catalytic subunit of chromosomal passenger complex with INCENP, Survivin, Borealin resides at inner centromere until metaphase and midbody during cytokinesis. It phosphorylates Ndc80/Hec1, MCAK, Dam1/Ska complexes to destabilize attachments lacking tension, thereby correcting errors. Polo-like kinases, typified by Plk1, contain C-terminal Polo-box domains binding phosphoserine motifs created by CDK1 priming, targeting them to kinetochores, centrosomes and central spindle. Plk1 phosphorylates pericentrin, Bub1, CLASP, PRC1 and ECT2 RhoGEF promoting centrosome maturation, kinetochore-microtubule stabilization, APC/C activation and cytokinesis. Combined activities ensure centrosome duplication limited to once per cycle, bipolar spindle assembly, chromosome biorientation and orderly exit. Dual Aurora and Plk inhibitors are studied in cancer therapy to induce mitotic arrest. 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.