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

J Cell Biol. 2002 Jul 22;158(2):235-46. doi: 10.1083/jcb.200203006. Epub 2002 Jul 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins
  • Endoplasmic Reticulum / metabolism*
  • Genes, p53*
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins
  • Proteins / genetics
  • Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation*

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Proteins
  • SHISA5 protein, human
  • Scotin protein, mouse
  • Transcription Factors