Skip to content
Login Register

#CDK1-Cyclin B

3 public questions tagged with this topic.

Cell Cycle Regulation

The mitotic CDK1-Cyclin B complex (MPF) is responsible for:

MPF converts interphase architecture into mitotic state through phosphorylation of hundreds of substrates. Nuclear entry of CDK1-Cyclin B, facilitated by phosphorylation of Cyclin B cytoplasmic retention sequence, allows access to chromatin proteins. Condensin I and II pentameric complexes containing SMC2, SMC4 become phosphorylated at non-SMC subunits CAP-D2, D3, CAP-G, H2, activating ATP-dependent loop extrusion that folds 10nm fiber into 700 nm wide rod chromosomes. Lamins phosphorylated at Ser22 Ser392 disassemble intermediate filament meshwork leading to nuclear envelope breakdown and merging with endoplasmic reticulum. Golgi matrix proteins GRASP65 GM130 phosphorylated causing vesiculation and partitioning. Interphase microtubule array destabilized while centrosomal gamma-TuRC recruitment of pericentrin enhanced drives bipolar spindle formation after Eg5 kinesin activation and NuMA dynein redistribution. Transcription inhibition through TFIIH and TFIID phosphorylation silences gene expression. Together these modifications reconfigure cell for chromosome capture, alignment and segregation, all attributable to single CDK1-Cyclin B holoenzyme activity rising at mitotic onset and falling after anaphase due to cyclin B destruction. 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.

Ref: Hirano, Condensins and Mitotic Chromosome Architecture, Nat Rev Mol Cell Biol 2012; Alberts et al., Chapter 17, MPF Targets.

View Details
Cell Cycle Regulation

Which complex regulates the G2/M transition?

G2 to M transition represents bistable switch controlled by accumulation of active CDK1-Cyclin B, often termed mitosis-promoting factor. Throughout G2, Cyclin B synthesis steadily rises transcribed by FoxM1 and stabilized, yet associated CDK1 remains inactive due to inhibitory phosphorylations at Thr14 and Tyr15 catalyzed by nuclear Wee1 and cytoplasmic Myt1 kinases occupying ATP-binding pocket. At threshold, dual specificity phosphatase Cdc25B initially and subsequently Cdc25C removes these phosphates. Activating Thr161 phosphorylation by CAK complex CDK7-Cyclin H further boosts activity. Once small amount of CDK1-Cyclin B activates, it initiates powerful feedback circuits: phosphorylation and activation of Cdc25 isoforms generating positive feedback, and phosphorylation and inhibition of Wee1 plus degradation via SCF-betaTrCP producing double negative loop. Rapid autoamplification creates abrupt switch. Active CDK1-Cyclin B translocates into nucleus via importin beta and cyclin B nuclear localization signal phosphorylation, phosphorylating lamins, condensins, Golgi and microtubule motors orchestrating prophase. DNA damage checkpoint via ATR-Chk1 inhibits Cdc25 and stabilizes Wee1 to maintain G2 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.

Ref: Morgan, Cell Cycle Control Principles of G2/M Transition, Chapter 3; Alberts et al., Molecular Biology of the Cell, CDK1-Cyclin B Regulation.

View Details
Cell Cycle Regulation

Which of the following is NOT a function of CDK1-Cyclin B?

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.

Ref: Morgan, The Cell Cycle: Principles of Control, Chapter 3, Mitotic CDK Functions; Nature Reviews, Mitotic Entry and Mitosis.

View Details