APC/C-dependent degradation of geminin (GMNN) was first demonstrated in Xenopus (McGarry and Kirschner 1998) and was shown to be proteasome-dependent and sensitive to FBXO5 (Emi1)-mediated inhibition of the APC/C:Cdh1 activity in human cells (Machida and Dutta 2007).
From the end of anaphase and throughout G1, the Cdh1 (FZR1) containing anaphase-promoting complex (APC/C:Cdh1) ubiquitinates geminin (GMNN), targeting it for degradation and enabling release of CDT1 and the subsequent association of CDT1 with the replication origins.The presence of an APC destruction box in geminin and its APC/C-mediated ubiquitination and degradation was first demonstrated in Xenopus egg extracts (McGarry and Kirschner 1998) and was later confirmed in human cells, where it was shown to largely depend on Cdh1 and not Cdc20 component of the APC/C (Pfleger et al. 2001; Di Fiore and Pines 2007; Machida and Dutta 2007). Emi1 (FBXO5) mediated inhibition of the APC/C:Cdh1 complex in S and G2 phases is needed for stabilization of geminin and prevention of re-replication (Di Fiore and Pines 2007; Machida and Dutta 2007).