Role of CAS, a Human Homologue to the Yeast Chromosome Segregation Gene CSE1, in Toxin and Tumor Necrosis Factor Mediated Apoptosis

Biochemistry. 1996 May 28;35(21):6891-9. doi: 10.1021/bi952829+.

Abstract

We have previously isolated by expression/selection cloning plasmids containing human cDNAs that rendered MCF-7 breast cancer cells resistant to immunotoxins, Pseudomonas exotoxin (PE), and diphtheria toxin (DT) [Brinkmann et al. (1995) Mol. Med. 1, 206-216]. Here we describe that one of these resistant plasmids, which contains an antisense cDNA fragment homologous to the yeast chromosome segregation gene CSE1 [CAS; Brinkmann et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10427-10431], reduces the intracellular content of the human CSE1 homologue CAS protein. CAS reduction confers resistance not only to the ADP-ribosylating toxins PE and DT, but also to tumor necrosis factor alpha and beta. The resistance was observed as reduced apoptosis. CAS antisense did not affect the cell death induced by staurosporine, cycloheximide, or etoposide. The observation that CAS antisense can interfere with apoptosis mediated by TNF and ADP-ribosylating toxins suggests that CAS may play a role in selected pathways of apoptosis.

MeSH terms

  • ADP Ribose Transferases*
  • Adenosine Diphosphate Ribose / metabolism
  • Antibodies / pharmacology
  • Antigens, Polyomavirus Transforming / biosynthesis
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Bacterial Toxins*
  • Breast Neoplasms
  • Cell Line
  • Cellular Apoptosis Susceptibility Protein
  • DNA, Antisense / pharmacology
  • DNA, Neoplasm / drug effects
  • Diphtheria Toxin / toxicity*
  • Drug Resistance, Neoplasm
  • Exotoxins / toxicity*
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Library
  • Genes, Fungal*
  • HeLa Cells
  • Humans
  • Immunotoxins / toxicity*
  • Lymphotoxin-alpha / toxicity*
  • Nuclear Proteins*
  • Nucleocytoplasmic Transport Proteins
  • Peptide Elongation Factor 2
  • Peptide Elongation Factors / metabolism
  • Protein Biosynthesis
  • Proteins / antagonists & inhibitors
  • Proteins / metabolism*
  • Pseudomonas aeruginosa
  • Recombinant Fusion Proteins / toxicity
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / toxicity*
  • Virulence Factors*

Substances

  • Antibodies
  • Antigens, Polyomavirus Transforming
  • Bacterial Toxins
  • CSE1 protein, S cerevisiae
  • Cellular Apoptosis Susceptibility Protein
  • DNA, Antisense
  • DNA, Neoplasm
  • Diphtheria Toxin
  • Exotoxins
  • Fungal Proteins
  • Immunotoxins
  • Lymphotoxin-alpha
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Peptide Elongation Factor 2
  • Peptide Elongation Factors
  • Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Tumor Necrosis Factor-alpha
  • Virulence Factors
  • Adenosine Diphosphate Ribose
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa