Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein.
A common feature shared between several human cancer-associated viruses, such as Epstein-Barr virus, Hepatitis B virus and Hepatitis C virus, and Human papillomavirus (HPV) is the ability to reduce the expression of cellular E-cadherin. Since E-cadherin is used by Langerhans cells to move through the stratified epithelium, its reduction may affect the efficiency by which the immune system responds to HPV infection and the length of persistent HPV infections. We observed that the E7 protein of this virus (HPV16) is most efficient at reducing E-cadherin levels. This E7 activity is independent of retinoblastoma protein or AP-2alpha degradation. Instead it is associated with augmentation of cellular DNA methyltransferase I (Dnmt1) activity. Significantly, inhibition of Dnmt activity re-established E-cadherin levels of the cells, presenting the possibility that similar epigenetic intervention clinically may be a way to re-establish the influx of Langerhans cells into infected epithelium to counteract HPV persistence.
Laurson
Joanna
J
Department of Virology, The National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA, UK.
Khan
Sadaf
S
Chung
Rachel
R
Cross
Karen
K
Raj
Kenneth
K
D015820:Cadherins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D044127:Epigenesis, Genetic; D006801:Humans; D050725:Papillomavirus E7 Proteins / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000037:antagonists & inhibitors
D015820:Cadherins; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; D050656:Transcription Factor AP-2; C059731:oncogene protein E7, Human papillomavirus type 16; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human