Practice question

Cyclins earned name due to fluctuating concentrations through cell cycle while CDKs remain relatively constant. Function is to activate CDKs by allosteric remodeling and to direct substrate choice through additional binding motifs. In G1, Cyclin D with CDK4/6 senses mitogens, Cyclin E with CDK2 triggers S-phase entry, Cyclin A with CDK2 drives S-phase progression and later with CDK1 primes mitosis, Cyclin B with CDK1 executes mitosis. Each cyclin contains conserved cyclin box domain and hydrophobic patch recognizing RXL motifs on substrates, plus localization signals determining nuclear or centrosomal enrichment. Binding causes CDK PSTAIRE helix rotation aligning catalytic lysine glutamate salt bridge and opening activation segment for substrate accommodation. Resulting holoenzyme phosphorylates diverse targets including Rb family proteins for transcription derepression, lamins for envelope breakdown, condensins for chromosome compaction, replication factors for origin firing control and microtubule associated proteins for spindle assembly. Ubiquitination by SCF in interphase and APC/C in mitosis ensures periodic disappearance of cyclins, creating irreversible forward direction. Thus cyclins convert basal low affinity kinase into temporal specific effector.