Tales of Survival

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Science  01 Apr 2005:
Vol. 308, Issue 5718, pp. 19
DOI: 10.1126/science.308.5718.19e

DJ-1 is an intensely studied but mysterious gene with links to two human diseases. Originally identified as a collaborator of the H-ras oncogene in conferring tumorigenic properties on normal cells in culture, DJ-1 was subsequently found to be mutated in a hereditary form of Parkinson's disease. Although this discovery triggered a flurry of research on the mechanistic roles of DJ-1 in neurodegenerative disease, progress on that front has been slow.

Kim et al. revisit the question of how DJ-1 contributes to tumor formation and show that the DJ-1 protein is expressed at aberrantly high levels in human breast and lung cancers and that the DJ-1 gene negatively regulates an important tumor suppressor gene called PTEN. In so doing, DJ-1 appears to activate a key cell survival pathway that is normally inhibited by PTEN, thereby preventing the death of tumor cells. Interestingly, another gene recently found to be mutated in hereditary Parkinson's disease, PINK1 (Valente et al., Reports, 21 May 2004, p. 1158), was originally identified as a gene induced by PTEN, raising the possibility that dysregulation of this critical cell survival pathway may underlie both diseases. — PAK

Cancer Cell 7, 263 (2005).

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