Human Papillomavirus Type 16 E6 Protein Interacts with Cystic Fibrosis Transmembrane Regulator-associated Ligand and Promotes E6-associated Protein-mediated Ubiquitination and Proteasomal Degradation.
From: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Oncogene
- Publish Date: Jan 2007
- ISSN: 0950-9232
- Volume: 26
- Issue: 4
- Pages: 487-99
- Medium: Print
- Language: English
- Citation (JAMA): Jeong K W, Kim H-Z, Kim S, et al. Human Papillomavirus Type 16 E6 Protein Interacts with Cystic Fibrosis Transmembrane Regulator-associated Ligand and Promotes E6-associated Protein-mediated Ubiquitination and Proteasomal Degradation.. Oncogene Jan 2007;26:487-99
Abstract
The PDZ proteins such as hDLG, hScrib and MAGIs function as the membrane-associated protein scaffolds and have been shown to interact with the high-risk human papillomavirus (HPV) E6s. In this report, we identify a Golgi-associated PDZ protein, cystic fibrosis transmembrane regulator-associated ligand (CAL) as a cellular target of HPV16 E6 by the proteomic approach. The carboxy-terminal PDZ-binding motif of HPV16 E6 specifically interacts with the PDZ domain of CAL, and the interaction enhances proteasome-mediated degradation of CAL. HPV16 E6 interacts with CAL more strongly and degrades it better than HPV18 E6 owing to the more compatible PDZ-binding motif. CAL is ubiquitinated by the E6/E6-associated protein (E6AP) complex or by E6AP alone, albeit less efficiently, which indicates that it could be a normal target of E6AP. Although it downregulates CAL at the transcript level, small interfering RNA-induced depletion of HPV16 E6 in Caski cells stabilizes CAL at the protein level, suggesting that HPV16 E6 mediates the proteasomal degradation of CAL in HPV-positive cervical cancer cells. HPV16 E6 may tightly regulate the vesicular trafficking processes by interacting with CAL, and such a modification can contribute to the development of cervical cancer.
Mesh Headings (Keywords): Carrier Proteins, Cells, Cultured, Humans, Membrane Proteins, Oncogene Proteins, Viral, Proteasome Endopeptidase Complex, Protein Binding, Protein Denaturation, Protein Structure, Tertiary, RNA, Small Interfering, Repressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases
Check for Full Text / PubMed Unique Identifier (PMID): 16878151
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