title: HIV's Nef interacts with β-catenin of the Wnt signaling pathway in HEK293 cells.
abstract: The Wnt signaling pathway is implicated in major physiologic cellular functions, such as proliferation, migration, cell fate specification, maintenance of pluripotency and induction of tumorigenicity. Proliferation and migration are important responses of T-cells, which are major cellular targets of HIV infection. Using an informatics screen, we identified a previously unsuspected interaction between HIV's Nef protein and β-catenin, a key component of the Wnt pathway. A segment in Nef contains identical amino acids at key positions and structurally mimics the β-catenin binding sites on endogenous β-catenin ligands. The interaction between Nef and β-catenin was confirmed in vitro and in a co-immunoprecipitation from HEK293 cells. Moreover, the introduction of Nef into HEK293 cells specifically inhibited a Wnt pathway reporter.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Keren
authors.initials: K
authors.lastname: Weiser
authors.forename: Meredith
authors.initials: M
authors.lastname: Barton
authors.forename: Dafna
authors.initials: D
authors.lastname: Gershoony
authors.forename: Ramanuj
authors.initials: R
authors.lastname: Dasgupta
authors.forename: Timothy
authors.initials: T
authors.lastname: Cardozo
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D057809:HEK293 Cells; D006678:HIV / Q000737:chemistry / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D054311:nef Gene Products, Human Immunodeficiency Virus