IFNα 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 IFNa 2b on a human small cell lung carcinoma (SCLC) cell line H82. We have found that IFNa efficiently induces apoptosis in H82 cells. The induction of apoptosis by IFNa 2b is accompanied by decreased levels of c-myc and Cdk2. We have also observed that in H82 cells IFNa 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. IFNa-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, IFNa 2b induces degradation of p27 Kip1 independently of CDK2 kinase activity and through a ubiquitin or ubiquitin-related pathway and that the degradation of p27 Kip1 could be a molecular event of importance for IFN-induced apoptosis in cancer cells.