FAT10: a novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy.
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.
Snyder
Alexandra
A
Mount Sinai School of Medicine, Division of Nephrology, Box 1243, 1 Gustave L Levy Place, New York, New York 10029, USA.
Alsauskas
Zygimantas
Z
Gong
Pengfei
P
Rosenstiel
Paul E
PE
Klotman
Mary E
ME
Klotman
Paul E
PE
Ross
Michael J
MJ
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*
C109184:UBD protein, human; D014452:Ubiquitins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1