Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins.
Ultraviolet B (UVB) damage is recognized as the most important etiological factor in the development of skin cancer. Human papillomaviruses (HPV) have also been implicated in the disease, although the mechanism of action of these viruses remains unknown. We present evidence here that Bak protein is involved in signaling apoptosis in the skin in response to UVB damage, and that cutaneous HPV E6 proteins target and abrogate Bak function by promoting its proteolytic degradation both in vitro and in regenerated epithelium. Additionally, HPV positive skin cancers had undetectable levels of Bak in contrast to HPV negative cancers, which expressed Bak. This study supports a link between the virus and UVB in the induction of HPV-associated skin cancer and reveals a survival mechanism of virally infected cells.
Jackson
S
S
Imperial Cancer Research Fund, Skin Tumour Laboratory, Centre for Cutaneous Research, London E1 2AT, UK.
Harwood
C
C
Thomas
M
M
Banks
L
L
Storey
A
A
D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein