Identification of a candidate therapeutic autophagy-inducing peptide
Autor(es): Shoji-Kawata Sanae, Sumpter Rhea, Leveno Matthew, Campbell Grant R, Zou Zhongju, Kinch Lisa, Wilkins Angela D, Sun Qihua, Pallauf Kathrin, MacDuff Donna, Huerta Carlos, Virgin Herbert W, Helms J Bernd, Eerland Ruud, Tooze Sharon A, Xavier Ramnik, Lenschow Deborah J, Yamamoto Ai, King David, Lichtarge Olivier, Grishin Nick V, Spector Stephen A, Kaloyanova Dora V, Levine Beth
Resumo: The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer - ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, - interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates - the replication of several pathogens (including HIV-1) in vitro, - reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.
Imprenta: Nature, v. 494, n. 7436, p. 201-206, 2013
Identificador do objeto digital: 10.1038/nature11866
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Flaviviridae ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus
Data de publicação: 2013
