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© The Rockefeller University Press, 0021-9525/2002/7/235 $5.00
The Journal of Cell Biology, Volume 158, Number 2, July 22, 2002 235-246

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

Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Cancer Research Campaign (CRC) Cell Transformation Research Group, University of Dundee, Dundee DD1 9SY, UK

Address correspondence to D.P. Lane, Dept. of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, CRC Cell Transformation Research Group, University of Dundee, Dundee DD1 9SY, UK. Tel.: 44-1382-496362. Fax: 44-1382-496363. E-mail: j.bourdon{at}dundee.ac.uk

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 -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.

Key Words: transactivation; p53-binding site; cell death; cancer; 3p21

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