title: HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels.
abstract: BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, we investigated the possible role of Tat protein in modulating BAG3 protein levels and the autophagic process itself. In this report, we show that transfection with Tat raises BAG3 levels in glioblastoma cells. Moreover, BAG3 silencing results in highly reducing Tat- induced levels of LC3-II and increasing the appearance of sub G0/G1 apoptotic cells, in keeping with the reported role of BAG3 in modulating the autophagy/apoptosis balance. These results demonstrate for the first time that Tat protein is able to stimulate autophagy through increasing BAG3 levels in human glial cells.
authors.affiliation: a Department of Pharmacy ; University of Salerno ; via Giovanni Paolo II; Fisciano , Italy.
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Bruno
authors.forename: Francesca Isabella
authors.initials: FI
authors.lastname: De Simone
authors.forename: Vittoria
authors.initials: V
authors.lastname: Iorio
authors.forename: Margot
authors.initials: M
authors.lastname: De Marco
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Ilker Kudret
authors.initials: IK
authors.lastname: Sariyer
authors.forename: Mario
authors.initials: M
authors.lastname: Capunzo
authors.forename: Stefania Lucia
authors.initials: SL
authors.lastname: Nori
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: BAG3; BAG3, Bcl-2-Associated Athanogene 3; HIV-1; LC3, microtubule-associated protein 1 light chain 3; Tat; Tat, Trans-Activator of Transcription;; autophagy; glioblastoma