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The tumor suppressor p53 can act as a transcription factor, but only a few p53-activated genes have been found, and the biochemical basis of p53-mediated apoptosis has been especially difficult to probe. Now, Bourdon et al. describe the discovery and characterization of a novel p53-inducible proapoptotic gene (page 235).* E6 {: c0 ~. }2 s/ d
d. r$ e9 E$ mBy comparing gene expression in normal and p53-knockout mice exposed to ionizing radiation, the authors identified Scotin, a novel gene that is directly trans-activated when p53 binds to a specific site in its promoter. Mouse Scotin and its human homologue appear to induce apoptosis in a caspase-dependent manner.
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Scotin has the structure of a type I transmembrane receptor, but is located in the endoplasmic reticulum and the nuclear membrane, not in the Golgi apparatus, mitochondria, or plasma membrane. The authors are now trying to determine whether this localization pattern is required for Scotin activity, and whether the protein can promote apoptosis in response to endoplasmic reticulum stress as well as DNA damage.
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The chromosomal location of the human Scotin gene, 3p21.3, is also tantalizing, as this region is rearranged or deleted in a wide range of human tumor types. Bourdon et al. found a dominant–negative phenotype in Scotin mutants, indicating that a mutation in a single allele of the gene could be sufficient to block the apoptotic activity of the protein. In preliminary studies focusing on breast cancer, researchers have already found mutations in Scotin in tumors from several patients, suggesting that Scotin may be a clinically important new tumor suppressor gene.(The location of Scotin (green) suggests ) |
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发表于 2009-3-6 00:08
发表于 2015-5-31 17:01
