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Updated: Aug 10, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
HPV16 E1--E4 protein is phosphorylated by Cdk2/cyclin A and relocalizes this complex to the cytoplasm
Clare E Davy1, Mahmood Ayub, Deborah J Jackson
1Division of Virology, MRC National Institute for Medical Research, London NW7 1AA, UK. cdavy@nimr.mrc.ac.uk
Abstract:
The human papillomavirus type 16 E1--E4 protein is expressed abundantly in cells supporting viral DNA amplification, but its expression is lost during malignant progression. In cell culture, 16E1--E4 causes G2 cell cycle arrest by associating with and preventing the nuclear entry of Cdk1/cyclin B1 complexes. Here, we show that 16E1--E4 is also able to associate with cyclin A and Cdk2 during the G2 phase of the cell cycle. Only a weak association was apparent during S-phase, and progression through S-phase appeared unaffected. As with cyclin B1, the interaction of 16E1--E4 with cyclin A is dependent on residues T22/T23 and results in the accumulation of cyclin A in the cytoplasm where it colocalizes with 16E1--E4. 16E1--E4 serine 32 was found to be phosphorylated by Cdk2/cyclin A. We hypothesize that the interaction of 16E1--E4 with cyclin A may serve to increase the efficiency with which 16E1--E4 is able to prevent mitotic entry.
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