CENP-O Activators

Chemical activators of CENP-O play a significant role in the modulation of its activity during cell division. Paclitaxel and Taxol, sharing the same CAS number, are two such chemicals that stabilize microtubules. This stabilization is crucial as it enhances CENP-O's role in the maintenance of the kinetochore-microtubule attachments, which are essential for accurate chromosome segregation. Similarly, S-Trityl-L-cysteine acts by inhibiting mitotic spindle dynamics, which indirectly necessitates an increase in CENP-O activity to ensure correct chromosome alignment and secure segregation. The arrest of cells in mitosis by Monastrol, which inhibits kinesin Eg5, also results in an upregulation of CENP-O function. This upregulation helps to maintain the attachment of chromosomes to the mitotic spindle, thus reinforcing its activity in response to mitotic stress.

On the other hand, Nocodazole disrupts microtubule polymerization, affecting spindle formation and compelling CENP-O to stabilize kinetochore-microtubule interactions during the activation of the spindle assembly checkpoint. MG-132's role as a proteasome inhibitor leads to the accumulation of cell cycle proteins, including CENP-O, preventing its degradation and enhancing kinetochore stability. Inhibition of Aurora kinases by ZM447439 and Alisertib increases the requirement for CENP-O's correctional activity for kinetochore-microtubule attachment errors. SP600125's inhibition of JNK, BI2536's inhibition of Plk1, and Purvalanol A's inhibition of cyclin-dependent kinases result in cell cycle arrest situations where the role of CENP-O becomes more pronounced in maintaining chromosome alignment and segregation. Lastly, Colchicine binds to tubulin to prevent microtubule polymerization, leading to a condition where the activation of CENP-O is imperative to maintain the kinetochore-microtubule attachments necessary for proper cell cycle progression. Each of these chemicals, by disrupting normal cell cycle events, necessitates a heightened role for CENP-O to ensure the fidelity of chromosome segregation.