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.
Bourdon
J-C
JC
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, Scotland, UK. j.bourdon@dundee.ac.uk
Renzing
J
J
Robertson
P L
PL
Fernandes
K N
KN
Lane
D P
DP
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D016158:Genes, p53; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; C462779:SHISA5 protein, human; C462780:Scotin protein, mouse; D014157:Transcription Factors