Mutual inactivation of two RING-finger-type E3 ubiquitin ligases during cell cycle progression.

CRL and APC/C belong to the RING-finger-type E3 ligases, and both play important roles in cell cycle regulation. Recently, we found that SAG, a RING component of CRL, acts as an endogenous inhibitor of APC/C by competing with APC2 for E2s binding; while APC/CCDH1 targets SAG for ubiquitylation and degradation at G1 phase. The negative crosstalk between these two E3s ensures the orderly cell cycle progression.