title: 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.
authors.affiliation: Molecular Cell Biology Laboratory, The Smurfit Institute of Genetics, Trinity College, Dublin, Ireland. martinsj@tcd.ie
authors.forename: Seamus J
authors.initials: SJ
authors.lastname: Martin
mesh_terms: D001343:Autophagy; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009857:Oncogenes / Q000235:genetics*
chemical_list: D008565:Membrane Proteins