Identification of a Candidate Therapeutic Autophagy-inducing Peptide

Overview

Journal Nature

Specialty Science

Date 2013 Feb 1

PMID 23364696

Citations 430

Authors

Sanae Shoji-Kawata

Rhea Sumpter

Matthew Leveno

Grant R Campbell

Zhongju Zou

Lisa Kinch

Angela D Wilkins

Qihua Sun

Kathrin Pallauf

Donna MacDuff

Carlos Huerta

Herbert W Virgin

J Bernd Helms

Ruud Eerland

Sharon A Tooze

Ramnik Xavier

Deborah J Lenschow

Ai Yamamoto

David King

Olivier Lichtarge

Nick V Grishin

Stephen A Spector

Dora V Kaloyanova

Beth Levine

Affiliations

Soon will be listed here.

Abstract

The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and 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, and 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 and the replication of several pathogens (including HIV-1) in vitro, and 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.

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