Degradation of Tyrosine Phosphatase PTPN3 (PTPH1) by Association with Oncogenic HumanPapillomavirus E6 Proteins
| Autor: | Michael Kinter, Nicole Brimer, Ming Jing, Scott B. Vande Pol, Joanna Bohl |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
HECT domain
Ubiquitin-Protein Ligases medicine.medical_treatment Molecular Sequence Data Immunology PDZ domain Protein tyrosine phosphatase In Vitro Techniques Ligands Microbiology Transformation and Oncogenesis Receptor tyrosine kinase Cell Line chemistry.chemical_compound Growth factor receptor Virology medicine Humans Amino Acid Sequence Human papillomavirus 16 Binding Sites Base Sequence biology Growth factor Protein Tyrosine Phosphatase Non-Receptor Type 3 Tyrosine phosphorylation DNA Oncogene Proteins Viral Recombinant Proteins Protein Structure Tertiary Ubiquitin ligase Repressor Proteins Biochemistry chemistry Multiprotein Complexes Insect Science biology.protein Protein Tyrosine Phosphatases |
| Zdroj: | Journal of Virology. 81:2231-2239 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01979-06 |
| Popis: | Oncoproteins from DNA tumor viruses associate with critical cellular proteins to regulate cell proliferation, survival, and differentiation.Human papillomavirus (HPV) E6 oncoproteins have been previously shown to associate with a cellular HECT domain ubiquitin ligase termed E6AP (UBE3A). Here we show that the E6-E6AP complex associates with and targets the degradation of the protein tyrosine phosphatase PTPN3 (PTPH1) in vitro and in living cells. PTPN3 is a membrane-associated tyrosine phosphatase with FERM, PDZ, and PTP domains previously implicated in regulating tyrosine phosphorylation of growth factor receptors and p97 VCP (valosin-containing protein, termed Cdc48 in Saccharomyces cerevisiae ) and is mutated in a subset of colon cancers. Degradation of PTPN3 by E6 requires E6AP, the proteasome, and an interaction between the carboxy terminus of E6 and the PDZ domain of PTPN3. In transduced keratinocytes, E6 confers reduced growth factor requirements, a function that requires the PDZ ligand of E6 and that can in part be replicated by inhibiting the expression of PTPN3. This report demonstrates the potential of E6 to regulate phosphotyrosine metabolism through the targeted degradation of a tyrosine phosphatase. |
| Databáze: | OpenAIRE |
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