Similarly, overexpression of the APC/C substrate Skp2, an integral component of the SCF ubiquitin ligases that coordinate S-phase entry through the timely destruction of the p21CIP1/WAF1 and p27KIP1 cyclin-dependent kinase inhibitors, can promote untimely entry into the S-phase and cell-cycle progression; Skp2 overexpression is observed in a number of human cancers with poor prognosis (Nakayama and Nakayama, 2005). This evidence concerns the gene CDKN1A and cancer.