Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell death.

Abstract:

:Although Beclin 1 and mTOR are considered to be the main molecules to modulate the autophagic process, searching for other autophagy-regulating molecules is still an ongoing challenge to scientists. Here we demonstrated that FoxO1, a forkhead O family protein, is a mediator of autophagy. Upon oxidative stress or serum starvation, endogenous FoxO1 was required for autophagy in human cancer cell lines, and this process was independent of FoxO1's transcriptional activity as well as mTOR or Beclin 1. In response to stress, FoxO1 dissociated from an NAD(+)-dependent histone deacetylase SIRT2 and FoxO1 thus became acetylated and in turn bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. In particular, cytosolic FoxO1 suppressed tumor xenograft growth in nude mice in an autophagy-dependent manner. Our studies provide evidence that cytosolic FoxO1-induced autophagy is associated with tumor suppression function.

journal_name

Autophagy

journal_title

Autophagy

authors

Zhao Y,Wang L,Yang J,Zhang P,Ma K,Zhou J,Liao W,Zhu WG

doi

10.4161/auto.6.7.13289

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

988-90

issue

7

eissn

1554-8627

issn

1554-8635

pii

13289

journal_volume

6

pub_type

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