Fig. 4: Examples of cross talk between CRLs and APC/C complex ligases for efficient cell cycle progression.
From: Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases
CRL1SKP2 activity is suppressed by APC/CCDH1 in G1, but during the G1/S transition, Cyclin E/CDK2 inactivates APC/CCDH1, leading to the accumulation of SKP2. CRL1SKP2 and Cyclin-CDK activation of E2Fs promotes EMI1 expression, leading to APC/C inhibition throughout the S phase. The capacity of CRL1FBXW7 to target Cyclin E for destruction can affect APC/C activity. APC/C and CRL1Cyclin F form a reciprocal feedback loop controlling cell cycle progression, with Cyclin F and CDH1 antagonizing each other. Cyclin F is targeted for ubiquitination and degradation by APC/CCDH1 in the G1 phase, while CDH1 itself is a substrate of CRL1Cyclin F in the S phase. BUB3 prevents premature chromosome segregation by blocking APC/C from associating with its coactivator CDC20. Prior to entry into metaphase, CRL4RBBP7 targets BUB3 for degradation, allowing APC/C activation. WEE1, a negative regulator of APC/CCDC20, is targeted for degradation by CRL1β-TrCP in a Cyclin B1/CDK1-dependent manner. Substrates targeted by CRLs are symbolized with green inhibition symbols (see text for details).
