Fig. 2: Depiction of key proteins targeted by CRLs during cell cycle progression.
From: Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases
CDK complexes drive cell cycle progression. CDK levels remain stable throughout the cell cycle phases, whereas fluctuations in the levels of CDK activators (CDC25A/B and cyclins) and inhibitors (p21, p27, and p57) cause changes in CDK activities. Thus, CRL-mediated destruction of CDK-regulating proteins allows the disassembly and assembly of different cyclin-CDK complexes in the cell cycle phases (transfer from the CDK2-Cyclin E complex in S phase to CDK2-Cyclin A in G2 phase and from CDK1-Cyclin in G2 phase to CDK1-Cyclin B in M phase). CRLs also control cell cycle progression by the degradation of pocket proteins such as RB and p130, in turn promoting the activation of E2F transcription factors and the expression of genes needed for subsequent phases of the cell cycle, including EMI1, Cyclin A, and Cyclin E. In late S, E2Fs are targeted for destruction by CRL1, promoting cell cycle progression to G2 while preventing premature S-phase entry. Substrates targeted by CRLs are symbolized with green inhibition symbols. CRLs with superscripts denote the specific CRL-receptor complexes involved is a particular pathway. The “+” sign denotes CDK activation by CDC24A/B (by dephosphorylation).
