Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1.
We recently isolated human cDNA fragments that render MCF-7 breast cancer cells resistant to cell death caused by Pseudomonas exotoxin, Pseudomonas exotoxin-derived immunotoxins, diphtheria toxin, and tumor necrosis factor. We report here that one of these fragments is an antisense fragment of a gene homologous to the essential yeast chromosome segregation gene CSE1. Cloning and analysis of the full-length cDNA of the human CSE1 homologue, which we name CAS for cellular apoptosis susceptibility gene, reveals a protein coding region with similar length (971 amino acids for CAS, 960 amino acids for CSE1) and 59% overall protein homology to the yeast CSE1 protein. The conservation of this gene indicates it has an important function in human cells consistent with the essential role of CSE1 in yeast. CAS is highly expressed in human tumor cell lines and in human testis and fetal liver, tissues that contain actively dividing cells. Furthermore, CAS expression increases when resting human fibroblasts are induced to proliferate and decreases when they are growth-arrested. Thus, CAS appears to play an important role in both toxin and tumor necrosis factor-mediated cell death, as well as in cell proliferation.
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms; D002455:Cell Division; D002460:Cell Line; D029563:Cellular Apoptosis Susceptibility Protein; D015825:Chromosomes, Fungal; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D005333:Fetus; D005656:Fungal Proteins / Q000235:genetics*; D015870:Gene Expression; D005800:Genes, Fungal; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured
C082274:CSE1 protein, S cerevisiae; D029563:Cellular Apoptosis Susceptibility Protein; D018076:DNA, Complementary; D005656:Fungal Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins