Mutational analysis of the discs large tumour suppressor identifies domains responsible for human papillomavirus type 18 E6-mediated degradation
| Autor: | Silvina Galizzi, Lawrence Banks, Daniela Gardiol |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Proteasome Endopeptidase Complex
Mutant Cell PDZ domain DNA Mutational Analysis Biology law.invention Cell Line Discs Large Homolog 1 Protein law Multienzyme Complexes Virology medicine Humans Genes Tumor Suppressor Human papillomavirus Papillomaviridae Adaptor Proteins Signal Transducing fungi Membrane Proteins Proteins Oncogene Proteins Viral Protein Structure Tertiary Mutational analysis DNA-Binding Proteins Cysteine Endopeptidases medicine.anatomical_structure Proteasome Cell culture Suppressor |
| Zdroj: | The Journal of general virology. 83(Pt 2) |
| ISSN: | 0022-1317 |
| Popis: | The discs large (Dlg) tumour suppressor protein is targeted for ubiquitin-mediated degradation by the high-risk human papillomavirus E6 proteins. To understand further the mechanisms behind this, a mutational analysis of Dlg was undertaken. This study demonstrates that an intact PDZ domain 2 (PDZ2) on Dlg is necessary for the ability of E6 to bind and degrade Dlg. However, additional residues within the amino-terminal portion of Dlg are also required for optimal E6 activity. Stable cell lines expressing different Dlg mutants were also established and these confirm that Dlg is regulated intrinsically by the proteasome in the absence of E6; however, in this case, the sequences responsible for regulating Dlg stability lie predominantly within PDZ2. These results suggest that there are at least two mechanisms for regulating Dlg protein stability and that the pathways used by E6 are not necessarily the same as those used in the cell in its absence. |
| Databáze: | OpenAIRE |
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