Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane

p53 is a transcription factor that induces growth arrest or Apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after gamma-irradiation of whole Animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce Apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent Apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent Apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent Apoptosis.