Contributes to multiple aspects of the viral life cycle including viral genome amplification, suppression of suprabasal cell differentiation and egress of newly formed virions. Induces host cell cycle arrest at the G2 phase by associating with and preventing the nuclear entry of host CDK1/cyclin B1 complexes. Inhibits cellular DNA replication by preventing loading of host replication licensing proteins MCM2 and MCM7 onto chromatin. Within the cytoplasm, associates with host kinase SRPK1, a splicing factor regulator, and inhibits its activity. Therefore, E4 favors expression of late viral transcripts by inhibiting SRPK1-mediated phosphorylation of host serine-arginine (SR) proteins that have critical roles in mRNA metabolism. Late in the infectious cycle, E4 also acts to diminish the integrity of the keratinocyte by disrupting the keratin cytoskeleton and inducing apoptosis through alteration of mitochondrial function to facilitate egress of the newly formed virions. Assembles into oligomeric complexes. Interacts with host CDK1. Interacts with host SRPK1; this interaction may favor expression of late viral transcripts. Interacts with host cytokeratin components KRT8 and KRT18. Phosphorylated by host ERK. The phosphorylation triggers a structural change that enhances keratin binding and protein stability. The major E4 form is first synthesized as an E1^E4 fusion protein from spliced E1^E4 transcripts, such that the first few amino acids of the E4 protein are derived from the N terminus of E1. Belongs to the papillomaviridae E4 protein family.