PathwayStep4564 PathwayStep4565 PathwayStep4562 PathwayStep4563 PathwayStep4567 PathwayStep4566 PathwayStep4569 PathwayStep4568 PathwayStep4532 PathwayStep4531 PathwayStep4542 PathwayStep4538 Translocation of p27 to the nucleoplasm Translocation of p21 to the nucleus Formation of Cyclin A:Cdk2 complexes Translocation of Cyclin A:Cdk2 complexes to the nucleus Phosphorylation of Cyclin A:Cdk2 at Tyr 15 Cdc25A mediated dephosphorylation of Cyclin A:phospho-Cdk2 CAK-mediated phosphorylation of Cyclin A:Cdk2 Cyclin A:Cdk2 mediated phosphorylation of p27/p21 Inactivation of Cyclin A:Cdk2 complexes by p27/p21 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2 Activation of Cdc25A by c-myc Cyclin A:Cdk2-associated events at S phase entry Authored: Pagano, M, 2006-09-19 08:23:10 Cyclin A:Cdk2 plays a key role in S phase entry by phosphorylation of proteins including Cdh1, Rb, p21 and p27. During G1 phase of the cell cycle, cyclin A is synthesized and associates with Cdk2. After forming in the cytoplasm, the Cyclin A:Cdk2 complexes are translocated to the nucleus (Jackman et al.,2002). Prior to S phase entry, the activity of Cyclin A:Cdk2 complexes is negatively regulated through Tyr 15 phosphorylation of Cdk2 (Gu et al., 1995) and also by the association of the cyclin kinase inhibitors (CKIs), p27 and p21. Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase (CAK) is required for the activation of the CDK2 kinase activity (Aprelikova et al., 1995). The entry into S phase is promoted by the removal of inhibitory Tyr 15 phosphates from the Cdk2 subunit of Cyclin A:Cdk2 complex by the Cdc25 phosphatases (Blomberg and Hoffmann, 1999) and by SCF(Skp2)-mediated degradation of p27/p21 (see Ganoth et al., 2001). While Cdk2 is thought to play a primary role in regulating entry into S phase, recent evidence indicates that Cdk1 is equally capable of promoting entry into S phase and the initiation of DNA replication (see Bashir and Pagano, 2005). Thus, Cdk1 complexes may also play a significant role at this point in the cell cycle. Edited: Matthews, L, 2006-09-29 14:05:42 Pubmed10454565 Pubmed11231585 Pubmed11907280 Pubmed1396589 Pubmed15014502 Pubmed7629134 Reactome Database ID Release 4369656 Reactome, http://www.reactome.org ReactomeREACT_9029 Reviewed: Coqueret, O, 2006-10-06 08:59:06 SCF(Skp2)-mediated degradation of p27/p21