title: FAT10: a novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy.
abstract: Human immunodeficiency virus (HIV)-associated nephropathy is a significant cause of morbidity and mortality in HIV-infected persons. Vpr-induced cell cycle dysregulation and apoptosis of renal tubular epithelial cells are important components of the pathogenesis of HIV-associated nephropathy (HIVAN). FAT10 is a ubiquitin-like protein that is upregulated in renal tubular epithelial cells in HIVAN. In these studies, we report that Vpr induces increased expression of FAT10 in tubular cells and that inhibition of FAT10 expression prevents Vpr-induced apoptosis in human and murine tubular cells. Moreover, we found that Vpr interacts with FAT10 and that these proteins colocalize at mitochondria. These studies establish FAT10 as a novel mediator of Vpr-induced cell death.
authors.affiliation: Mount Sinai School of Medicine, Division of Nephrology, Box 1243, 1 Gustave L Levy Place, New York, New York 10029, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Snyder
authors.forename: Zygimantas
authors.initials: Z
authors.lastname: Alsauskas
authors.forename: Pengfei
authors.initials: P
authors.lastname: Gong
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rosenstiel
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
authors.forename: Paul E
authors.initials: PE
authors.lastname: Klotman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ross
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D051379:Mice; D014452:Ubiquitins / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
chemical_list: C109184:UBD protein, human; D014452:Ubiquitins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1