Date published: 2025-9-11

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Clb2 Inhibitors

Clb2, a cyclin protein found in budding yeast Saccharomyces cerevisiae, plays a pivotal role in regulating the cell cycle, particularly during the G2 to M transition phase. Functionally, Clb2 forms complexes with cyclin-dependent kinases (CDKs), specifically Clb2-Cdc28 complexes, which drive cell cycle progression by phosphorylating target proteins involved in various cellular processes. Clb2-Cdc28 complexes promote entry into mitosis by phosphorylating key substrates that regulate nuclear envelope breakdown, spindle assembly, and chromosome segregation. Additionally, Clb2 is involved in the regulation of DNA replication, DNA repair, and spindle assembly checkpoint activation, ensuring the fidelity of cell division and genome stability. Through its pivotal role in cell cycle regulation, Clb2 coordinates the orderly progression of cell division events, ensuring proper cell growth and proliferation.

Inhibition of Clb2 activity represents a strategy for modulating cell cycle progression and arresting cell proliferation, particularly in cancer cells characterized by dysregulated cell cycle control. Mechanistically, inhibition of Clb2 can be achieved through various approaches, including interference with its binding to CDKs, disruption of its expression levels or post-translational modifications, or targeting its downstream signaling pathways. Small molecule inhibitors targeting the interaction between Clb2 and CDKs inhibits the formation of active Clb2-Cdc28 complexes, thereby inhibiting cell cycle progression and inducing cell cycle arrest. Additionally, strategies aimed at modulating the expression or stability of Clb2 or its regulators may attenuate Clb2 activity and impede cell cycle progression. Understanding the detailed mechanisms underlying Clb2 inhibition offers insights into the regulation of cell cycle dynamics and provides targets for intervention in diseases characterized by aberrant cell proliferation.

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