Published by AAAS autophagy regulation. Codogno’s team showed that one of these is PTEN, which inhibits a major cell growth stimulatory pathway and, as a result of that, a protein called TOR. Because TOR normally curbs autophagy, the process gets ramped up. Jin, Arnold Levine, and their colleagues have shown that the well-known tumor-suppressor gene p53 also increases autophagy by inhibiting TOR. And Adi Kimchi and her colleagues at the Weizmann Institute of Science in Rehovot, Israel, have found that the tumor suppressor known as DAPK (for death-associated protein kinase) is yet another autophagy stimulator. Conversely, many oncogenes appear to inhibit autophagy. Codogno and his colleagues have found that overactivity of the oncogene AKT curbs autophagy—the expected result because it promotes TOR activity. And last month in Washington, DC, at the annual meeting of the American Association for Cancer Research (AACR), John Cleveland of St. Jude Children’s Research Hospital in Memphis, Tennessee, presented as-yetunpublished data from his lab indicating that the carcinogenic effects of the well-known myc oncogene are at least partly due to its ability to decrease autophagy. The evidence, obtained in collaboration with Michael Kastan, also at St. Jude, includes the finding that myc activity suppresses the expression of ATG genes 8 and 9.“Oncogenes suppress autophagy during tumor development,” Cleveland concludes. Then there’s bcl-2, the gene that helped Beth Levine and her colleagues identify beclin-1. This oncogene promotes the survival of cancer cells by inhibiting apoptosis, a process by which dysfunctional cells kill themselves. Evidence published by Levine and her colleagues last September in Cell raises the possibility that bcl-2 prevents autophagic cell death as well. Although autophagy is often protective, it can kill cells in some circumstances; they essentially digest themselves to death. The researchers showed that binding of the Bcl-2 protein to the protein product of beclin-1 inhibits autophagy. Levine suggests that this suppression by Bcl-2 helps keep autophagy in check under normal conditions. But if bcl-2 activity is excessive, as it is in some cancers, the consequent suppression of autophagy could allow damaged cells to complete a cancerous transformation. Killing abnormal cells is not the only way that autophagy could protect against tumor development, however. Autophagy’s recycling ability can eliminate damaged cell components, especially organelles such as the mitochondria. Indeed, Klionsky says, it “is virtually the only way to get rid of whole organelles.” Getting rid of defective mitochondria, which release abnormally large amounts of DNA-damaging reactive oxygen species, could help protect cells against cancercausing mutations, Jin and others suggest.