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Cited by 460

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase

Sun, Qiming, Fan, Weiliang, Chen, Keling, Ding, Xiaojun, Chen, She, Zhong, Qing·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0810452105
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Abstract

Autophagy mediates the cellular response to nutrient deprivation, protein aggregation, and pathogen invasion in human. Dysfunction of autophagy has been implicated in multiple human diseases including cancer. The identification of novel autophagy factors in mammalian cells will provide critical mechanistic insights into how this complicated cellular pathway responds to a broad range of challenges. Here, we report the cloning of an autophagy-specific protein that we called Barkor (Beclin 1-associated autophagy-related key regulator) through direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex. Barkor shares 18% sequence identity and 32% sequence similarity with yeast Atg14. Elimination of Barkor expression by RNA interference compromises starvation- and rapamycin-induced LC3 lipidation and autophagosome formation. Overexpression of Barkor leads to autophagy activation and increased number and enlarged volume of autophagosomes. Tellingly, Barkor is also required for suppression of the autophagy-mediated intracellular survival of Salmonella typhimurium in mammalian cells. Mechanistically, Barkor competes with UV radiation resistance associated gene product (UVRAG) for interaction with Beclin 1, and the complex formation of Barkor and Beclin1 is required for their localizations to autophagosomes. Therefore, we define a regulatory signaling pathway mediated by Barkor that positively controls autophagy through Beclin 1 and represents a potential target for drug development in the treatment of human diseases implicated in autophagic dysfunction.

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Research works printed but not linked: 19

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  13. B Levine, V Deretic, Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev 7, 767–777 (2007).
  14. 10.1083/jcb.200309161 · DOI
  15. 10.1074/jbc.M509157200 · DOI · Paper page
  16. 10.1038/ng2032 · DOI · Paper page
  17. 10.1038/nature04723 · DOI · Paper page
  18. 10.4161/auto.1.1.1542 · DOI
  19. 10.1038/ncb1426 · DOI · Paper page

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Metadata

Authors
Sun, Q., Fan, W., Chen, K., Ding, X., Chen, S., & Zhong, Q.
Affiliations
  • Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and
  • National Institute of Biological Sciences, Beijing 102206, China
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2008-12-09
Volume
105
Issue
49
Pages
19211-19216
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0810452105
Cited by
460
References
6
Language
en

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