title: Interferon beta increases c-Myc proteolysis in mouse monocyte/macrophage leukemia cells.
abstract: Growth inhibitory activity of interferons (IFNs) has been attributed to several events. These include rapid induction of cyclin-dependent kinase inhibitors, such as those in the Cip/Kip and Ink 4 families and down-regulation of c-myc mRNA and c-Myc transcriptional activity. Here, we report an additional mechanism, involving regulation of Myc protein levels, through which type 1 IFN may halt proliferation of cells. This was discovered using a cell line which constitutively expresses c-myc from a retrovirus vector and which was reported to have undergone deletion of genes encoding the Ink 4 tumor suppressors p15 and p16. IFNbeta caused a reduction in the steady state level of c-Myc protein by increasing degradation through the 26S proteasome. Our data, as well as that of others, indicate that multiple levels of c-Myc expression can be affected by IFN treatment and this contributes to rapid growth arrest in the G1 phase of the cell cycle.
authors.affiliation: Leukemogenesis Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Hu
authors.forename: Juraj
authors.initials: J
authors.lastname: Bies
authors.forename: Linda
authors.initials: L
authors.lastname: Wolff
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D016899:Interferon-beta / Q000494:pharmacology*; D007938:Leukemia; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D041681:NIH 3T3 Cells; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016899:Interferon-beta