Common importin alpha specificity for papillomavirus E2 proteins

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Papillomaviruses infect keratinocytes and their reproduction is tied to differentiation of the skin. The E2 protein of papillomaviruses is a multifunctional early protein that binds specifically to the viral DNA to regulate genome transcription, replication, and segregation. All of these are nuclear events that require specific transport of E2 into the host nucleus. Nuclear localization signal (NLS) sequences have been mapped for several E2 proteins, and these sequences resemble motifs that interact with cellular transport adaptor molecules termed alpha importins. To determine which importins could carry E2 proteins, in vitro binding studies were performed with three different E2 proteins and the five ubiquitous alpha importins. The E2 proteins preferentially interacted with alpha importins 3 and 5, and showed very weak or no interaction with the other three widely expressed alpha importins (α1, α4, and α7). While all five alpha importins appear to be constitutively expressed in keratinocytes, during differentiation of a human keratinocyte line (HaCaT) we observed a specific increase in expression of alphas 3 and 5. This differentiation-specific increase in α3 and α5 expression suggests that preferential usage of these two importins by E2 may facilitate E2 nuclear uptake during terminal differentiation.