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The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy

Identifieur interne : 000035 ( Main/Merge ); précédent : 000034; suivant : 000036

The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy

Auteurs : Ketaki Ganti ; Justyna Broniarczyk ; Wiem Manoubi ; Paola Massimi ; Suruchi Mittal ; David Pim ; Anita Szalmas ; Jayashree Thatte ; Miranda Thomas ; Vjekoslav Tomai ; Lawrence Banks

Source :

RBID : PMC:4517114

Abstract

Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM) at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.


Url:
DOI: 10.3390/v7072785
PubMed: 26147797
PubMed Central: 4517114

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PMC:4517114

Le document en format XML

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<p>Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM) at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.</p>
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