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J Biol Chem. 2009 Jan 30;284(5):2803-10. doi: 10.1074/jbc.M804705200. Epub 2008 Dec 2.

ARF induces autophagy by virtue of interaction with Bcl-xl.

Author information

1
Division of Medical Sciences, the Smolensk State Medical Academy Graduate Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Abstract

The ARF tumor suppressor controls a well-described p53/Mdm2-dependent oncogenic stress checkpoint. In addition, ARF has recently been shown to localize to mitochondria, and to induce autophagy; however, this has never before been demonstrated for endogenous ARF, and the molecular basis for this activity of ARF has not been elucidated. Using an unbiased mass spectrometry-based approach, we show that mitochondrial ARF interacts with the Bcl2 family member Bcl-xl, which normally protects cells from autophagy by inhibiting the Beclin-1/Vps34 complex, which is essential for autophagy. We find that increased expression of ARF decreases Beclin-1/Bcl-xl complexes in cells, thereby providing a basis for ARF-induced autophagy. Our data also indicate that silencing p53 leads to high levels of ARF and increased autophagy, thereby providing a possible basis for the finding by others that p53 inhibits autophagy. The combined data support the premise that ARF induces autophagy in a p53-independent manner in part by virtue of its interaction with Bcl-xl.

PMID:
19049976
PMCID:
PMC2631963
DOI:
10.1074/jbc.M804705200
[Indexed for MEDLINE]
Free PMC Article

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