Common importin alpha specificity for papillomavirus E2 proteins.
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 (alpha1, alpha 4, and alpha 7). 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 alpha 3 and alpha 5 expression suggests that preferential usage of these two importins by E2 may facilitate E2 nuclear uptake during terminal differentiation.
Bian
Xue-Lin
XL
Department of Biology, College of Science, Texas A&M University, College Station, TX 77843, USA. jbian@tamu.edu
Wilson
Van G
VG
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011485:Protein Binding; D014764:Viral Proteins / Q000378:metabolism*; D028901:alpha Karyopherins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; C423142:KPNA1 protein, human; C106259:KPNA4 protein, human; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; D028901:alpha Karyopherins; C076036:oncogene protein E2, Human papillomavirus type 1