Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis

Yoshinori Takahashi, Domenico Coppola, Norimasa Matsushita, Hernani D. Cualing, Mei Sun, Yuya Sato, Chengyu Liang, Jae U. Jung, Jin Q. Cheng, James J. Mulé, W. Jack Pledger, Hong-Gang Wang

Research output: Contribution to journalArticle

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Abstract

Autophagy is an evolutionarily conserved 'self-eating' process. Although the genes essential for autophagy (named Atg) have been identified in yeast, the molecular mechanism of how Atg proteins control autophagosome formation in mammalian cells remains to be elucidated. Here, we demonstrate that Bif-1 (also known as Endophilin B1) interacts with Beclin 1 through ultraviolet irradiation resistance-associated gene (UVRAG) and functions as a positive mediator of the class III PI(3) kinase (PI(3)KC3). In response to nutrient deprivation, Bif-1 localizes to autophagosomes where it colocalizes with Atg5, as well as microtubule-associated protein light chain 3 (LC3). Furthermore, loss of Bif-1 suppresses autophagosome formation. Although the SH3 domain of Bif-1 is sufficient for binding to UVRAG, both the BAR and SH3 domains are required for Bif-1 to activate PI(3)KC3 and induce autophagosome formation. We also observed that Bif-1 ablation prolongs cell survival under starvation conditions. Moreover, knockout of Bif-1 significantly enhances the development of spontaneous tumours in mice. These findings suggest that Bif-1 joins the UVRAG-Beclin 1 complex as a potential activator of autophagy and tumour suppressor.

Original languageEnglish (US)
Pages (from-to)1142-1151
Number of pages10
JournalNature Cell Biology
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2007

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Autophagy
Carcinogenesis
src Homology Domains
Genes
Microtubule-Associated Proteins
Essential Genes
Starvation
Phosphatidylinositol 3-Kinases
Neoplasms
Cell Survival
Eating
Yeasts
Light
Food
Autophagosomes
Beclin-1
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Takahashi, Yoshinori ; Coppola, Domenico ; Matsushita, Norimasa ; Cualing, Hernani D. ; Sun, Mei ; Sato, Yuya ; Liang, Chengyu ; Jung, Jae U. ; Cheng, Jin Q. ; Mulé, James J. ; Pledger, W. Jack ; Wang, Hong-Gang. / Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. In: Nature Cell Biology. 2007 ; Vol. 9, No. 10. pp. 1142-1151.
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Takahashi, Y, Coppola, D, Matsushita, N, Cualing, HD, Sun, M, Sato, Y, Liang, C, Jung, JU, Cheng, JQ, Mulé, JJ, Pledger, WJ & Wang, H-G 2007, 'Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis', Nature Cell Biology, vol. 9, no. 10, pp. 1142-1151. https://doi.org/10.1038/ncb1634

Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. / Takahashi, Yoshinori; Coppola, Domenico; Matsushita, Norimasa; Cualing, Hernani D.; Sun, Mei; Sato, Yuya; Liang, Chengyu; Jung, Jae U.; Cheng, Jin Q.; Mulé, James J.; Pledger, W. Jack; Wang, Hong-Gang.

In: Nature Cell Biology, Vol. 9, No. 10, 01.10.2007, p. 1142-1151.

Research output: Contribution to journalArticle

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