6 Scopus citations


CDK2 activity is regulated by phosphorylation/dephosphorylation, subcellular localization, cyclin levels, and cyclin dependent kinase inhibitors (CKIs). Using Xenopus egg extracts, we find that degradation of Xicl, a Xenopus p21cip1/p27kip1 family member, is coupled to initiation of DNA replication. Xicl turnover requires the formation of a prereplication complex (pre-RC). Additionally, downstream initiation factors including CDK2, Cdc7, and Cdc45, but not RPA or DNA polymerase α, are necessary for activating the degradation system. Xicl degradation is attenuated following completion of DNA replication. Unlike degradation of p27kip1 in mammalian cells, CDK2 activity is not directly involved in Xic1 degradation and interactions between Xicl and CDK2/cyclin E are dispensable for Xicl turnover. Interestingly, a C-terminal region (162-192) of Xicl is essential and apparently sufficient for triggering Xicl ubiquitination prior to degradation. These observations demonstrate that a direct link exists between DNA replication and CKI degradation.

Original languageEnglish
Pages (from-to)1182-1194
Number of pages13
JournalGenes and Development
Issue number10
StatePublished - May 15 2002


  • CDK inhibitor
  • CDK2/cyclin E
  • Initiation of DNA replication
  • Xicl


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