Identification of a hTid-1 mutation which sensitizes gliomas to apoptosis

FEBS Lett. 2004 Dec 17;578(3):323-30. doi: 10.1016/j.febslet.2004.11.034.


Human Tid-1 (hTid-1) is a DnaJ chaperone protein with homology to the Drosophila tumor suppressor Tid56. We report the first case of a tumor-associated mutation at the human TID1 locus, which was identified in the SF767 glioma cell line giving rise to aberrantly high levels of a hTid-1(L) mutant variant. In this study, we set out to determine whether this change in hTid-1 status influences the response of glioma cells to adenoviral (Ad)-mediated delivery of the two major isoforms of TID1, hTid-1(L) and hTid-1(S). Ad-hTid-1(S) induced apoptosis in hTid-1 mutant SF767 cells, while causing growth arrest in wild-type hTid-1-expressing U373 and U87 cells. By contrast, Ad-hTid-1(L) infection had no apparent effect on glioma cell growth. The apoptosis induced by hTid-1(S) was accompanied by mitochondrial cytochrome C release and caspase activation and blocked by stable overexpression of Bcl-X(L). Our findings suggest that the status of hTid-1 in gliomas may contribute to their susceptibility to cell death triggers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / genetics*
  • Blotting, Western
  • COS Cells
  • Caspases / metabolism
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cytochrome c Group / metabolism
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Enzyme Activation
  • Genes, Tumor Suppressor*
  • Genetic Variation
  • Glioma
  • HSP40 Heat-Shock Proteins
  • Heat-Shock Proteins / genetics
  • Humans
  • Insect Proteins / genetics
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Mitochondrial Proteins
  • Molecular Chaperones / genetics*
  • Molecular Weight
  • Mutation*
  • Propidium
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-X Protein


  • BCL2L1 protein, human
  • CG5504 protein, Drosophila
  • Cytochrome c Group
  • DNAJA3 protein, human
  • Drosophila Proteins
  • HSP40 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Insect Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Propidium
  • Caspases