The effect of isoforms of the cell polarity protein, human ASIP, on the cell cycle and Fas/FasL-mediated apoptosis in human hepatoma cells.
Human ASIP (hASIP) is expressed as numerous alternative splicing isoforms and there is an atypical protein kinease C (aPKC) phosphorylation site in exon 17b of the encoded sequence. We have identified an important role for exon 17b in cancer cells. Our results showed that hASIP-sa and sb had different effects on cell growth and Fas/FasL-mediated apoptosis in BEL-7404 human hepatoma cells. Human ASIP-sa modified the S phase of the cell cycle and might stimulate cell proliferation. Growth inhibition by hASIP-a antisense oligonucleotide-confirmed the positive action of hASIP-sa. Compared with hASIP-sa, hASIP-sb accelerated Fas/FasL-induced apoptosis, examined by sub-G1 accumulation, chromatin condensation, nuclear fragmentation, PARP cleavage, caspase-8 degradation and mitochondria- regulated cell death. Treatment with aPKC inhibitor could enhance Fas/FasL-mediated apoptosis in hASIP-sa-overexpressing cells, suggesting that hASIP-sa and its interaction with aPKC might contribute to the malignant growth and the blocking of Fas/FasL-mediated apoptosis, while hASIP-sb might function as an antagonist of hASIP-sa.
Hu
Y
Y
Laboratory of Molecular and Cellular Oncology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China. yhxu@sibs.ac.cn
Fang
C
C
Xu
Y
Y
D054366:Agouti Signaling Protein; D017398:Alternative Splicing; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D016764:Cell Polarity; D005091:Exons / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D054366:Agouti Signaling Protein; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D019014:fas Receptor; D011493:Protein Kinase C