Identification of a candidate therapeutic autophagy-inducing peptide

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 LichtargeNick V. Grishin, Stephen A. Spector, Dora V. Kaloyanova, Beth Levine

Research output: Contribution to journalArticle

403 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalNature
Volume494
Issue number7436
DOIs
StatePublished - Feb 14 2013

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Identification of a candidate therapeutic autophagy-inducing peptide'. Together they form a unique fingerprint.

  • Cite this

    Shoji-Kawata, S., Sumpter, R., Leveno, M., Campbell, G. R., Zou, Z., Kinch, L., Wilkins, A. D., Sun, Q., Pallauf, K., MacDuff, D., Huerta, C., Virgin, H. W., Bernd Helms, J., Eerland, R., Tooze, S. A., Xavier, R., Lenschow, D. J., Yamamoto, A., King, D., ... Levine, B. (2013). Identification of a candidate therapeutic autophagy-inducing peptide. Nature, 494(7436), 201-206. https://doi.org/10.1038/nature11866