Oncogene-induced autophagy and the Goldilocks principle.

Abstract:

:Although several oncogenes enhance autophagic flux, the molecular mechanism and consequences of oncogene-induced autophagy remain to be clarified. We have recently shown that expression of oncogenic H-Ras (V12) promotes autophagy through upregulation of Beclin 1 and the BH3-only protein Noxa. H-Ras-expressing cells undergo autophagic cell death as a result of Noxa-mediated displacement of Mcl-1 and Bcl-xL from Beclin 1. Oncogenic H-Ras-induced death is attenuated through knockdown of BECLIN 1, ATG5, or ATG7, or through overexpression of Mcl-1, Bcl-2, Bcl-xL and their close relatives. These observations suggest that high-intensity oncogene activation may be selected against by promoting excessive autophagy, leading to cell death. Consequently, such oncogenes may select for cells with a reduced capacity for autophagy, either through loss of a BECLIN 1 allele or through upregulation of negative regulators of Beclin 1, such as Bcl-2 family members.

journal_name

Autophagy

journal_title

Autophagy

authors

Martin SJ

doi

10.4161/auto.7.8.15821

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

922-3

issue

8

eissn

1554-8627

issn

1554-8635

pii

15821

journal_volume

7

pub_type

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