IFNalpha 2b induces apoptosis and proteasome-mediated degradation of p27Kip1 in a human lung cancer cell line.
IFNs are a family of cytokines involved in antiviral defense, cell growth regulation and immune activation. IFNs either inhibit cell proliferation or control apoptosis depending on factors such as cell type and state of cell differentiation. It is important to determine how IFN-induced gene products interact with other cellular proteins to produce these responses. We have investigated the effect of IFNalpha 2b on a human small cell lung carcinoma (SCLC) cell line H82. We have found that IFNalpha efficiently induces apoptosis in H82 cells. The induction of apoptosis by IFNalpha 2b is accompanied by decreased levels of c-myc and Cdk2. We have also observed that in H82 cells IFNalpha induces downregulation of p27 and this is in contrast to the upregulation of p27 observed in other cell types where IFNs induce cell cycle arrest. IFNalpha-induced downregulation of p27 is due to protein destabilization and can be prevented by the proteasome inhibitor LLnL. The data suggest that in H82 cells, IFNalpha 2b induces degradation of p27Kip1 independently of CDK2 kinase activity and through a ubiquitin or ubiquitin-related pathway and that the degradation of p27Kip1 could be a molecular event of importance for IFN-induced apoptosis in cancer cells.
Moro
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Centro de Ingeniería Genética y Biotecnología, C.P 10600, Havana, Cuba. alejandro.moro@cigb.edu.cu
Perea
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SE
Pantoja
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Santos
A
A
Araña
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MD
Serrano
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M
D017209:Apoptosis / Q000187:drug effects*; D042846:CDC2-CDC28 Kinases; D018288:Carcinoma, Small Cell; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D016259:Genes, myc; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008175:Lung Neoplasms; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex