The Human Papillomavirus Type 16 E5 Protein Impairs TRAIL- and FasL-Mediated Apoptosis in HaCaT Cells by Different Mechanisms
| Autor: | Kirsten Kabsch, Angel Alonso |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Fas Ligand Protein
Immunology Apoptosis Caspase 3 Biology Transfection Caspase 8 Models Biological Microbiology Receptors Tumor Necrosis Factor Fas ligand Cell Line TNF-Related Apoptosis-Inducing Ligand Mice Virology Animals Humans fas Receptor Papillomaviridae Enzyme Precursors Membrane Glycoproteins Tumor Necrosis Factor-alpha Oncogene Proteins Viral Caspase 9 Virus-Cell Interactions Cell biology Receptors TNF-Related Apoptosis-Inducing Ligand HaCaT Cell culture Caspases Insect Science Tumor necrosis factor alpha Poly(ADP-ribose) Polymerases Apoptosis Regulatory Proteins |
| Zdroj: | Journal of Virology. 76:12162-12172 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.76.23.12162-12172.2002 |
| Popis: | The effect of the human papillomavirus type 16 (HPV-16) E5 protein on apoptosis was investigated by using the polyclonal HaCaT-cell lines stably transfected either with E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as reference. Apoptosis was triggered either by Fas ligand (FasL) or by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and was monitored by detection of cleavage of procaspase-8 and procaspase-3, as well as their substrate poly(ADP-ribose) polymerase (PARP). In contrast to the HaCaT/pMSG control cells we found that apoptosis induced by either of the two ligands is strongly suppressed in the E5-expressing keratinocytes. Fas expression is reduced by about a factor of two in HaCaT/E5 cells, which could be part of the mechanisms that protect the cells from FasL-induced apoptosis. For the TRAIL receptors, no such downregulation was observed. Here, E5 impairs the formation of the death-inducing signaling complex triggered by TRAIL. Apparently, E5 employs different mechanisms to inhibit death receptor signaling. This effect is not restricted to HaCaT/E5 cells since we found that the mouse fibroblast cell line A31-E5 is protected from TRAIL-induced apoptosis, as well but not the E5-lacking control cells A31-Neo. However, no such protection was observed upon FasL-induced apoptosis. Presumably, some of the antiapoptotic mechanisms employed by E5 of the human pathogenic HPV-16 are cell type specific. We propose that inhibition of ligand-mediated apoptosis in human keratinocytes is a primary function of the HPV-16 E5 protein needed to prevent apoptosis at early stages of viral infection. |
| Databáze: | OpenAIRE |
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